Search Results (937)

Background/Objectives: Cadherin-17 (CDH17, LI-cadherin) is a non-classical cadherin with an atypical structure and unique functions. CDH17 expression is restricted to normal intestinal epithelium. Furthermore, CDH17 functions as an oncoprotein that promotes tumor migration and invasion in colorectal, gastric, and pancreatic cancers. Therefore, CDH17 is an important diagnostic marker and therapeutic target. The CDH17-directed strategies, including monoclonal antibodies (mAbs), bispecific Abs, antibody–drug conjugates (ADCs), and chimeric antigen receptor (CAR) T cells, have been evaluated in preclinical and clinical studies. Therefore, developing mAbs that specifically recognize cell surface-expressing CDH17 is essential for advancing both tumor diagnosis and therapy. Methods: Anti-human CDH17 mAbs (named Ca₁₇Mabs) were developed by immunizing a mouse with CDH17-overexpressed cells and a high-throughput screening using flow cytometry. Results: Among Ca₁₇Mabs, a clone, Ca₁₇Mab-5 (IgG₁, κ) specifically recognized CDH17-overexpressed Chinese hamster ovary-K1 (CHO/CDH17) cells with no detectable cross-reactivity to 21 other CDHs by flow cytometry. Ca₁₇Mab-5 also detected endogenous CDH17 in human colorectal cancer cell lines, COLO201 and COLO205. The apparent dissociation constant (K_D) values of Ca₁₇Mab-5 for CHO/CDH17 and COLO205 were estimated as 1.5 × 10⁻⁸ M and 1.3 × 10⁻⁸ M, respectively. Furthermore, Ca₁₇Mab-5 detected endogenous CDH17 by Western blotting. In immunohistochemistry, Ca₁₇Mab-5 exhibited clear membranous staining in normal colon epithelium, colorectal, gastric, and pancreatic cancers. Conclusions: Ca₁₇Mab-5 is a versatile tool for detecting CDH17 and has potential for tumor diagnosis. Full article

Background: Chimeric antigen receptor (CAR) T-cell therapy has transformed haematological-malignancy care, but its dermatologic safety profile remains incompletely characterised across products and indications. Methods: We analysed 8,431,841 deduplicated FDA Adverse Event Reporting System reports from 2016 Q3 to 2026 Q1. Seven approved CAR T-cell products were identified. The primary outcome was any dermatologic adverse event, defined using the MedDRA Skin and subcutaneous tissue disorders system organ class. Secondary outcomes included broad severe cutaneous adverse reactions, narrow Stevens-Johnson syndrome/toxic epidermal necrolysis, and 14 phenotype-specific categories. Multivariable models adjusted for demographics, polypharmacy, cancer, immune checkpoint inhibitor exposure, lymphodepleting chemotherapy and cytokine release syndrome. Additional sensitivity analyses evaluated HSCT/GVHD co-reporting proxies, infection and cytopenia/bleeding proxies, severe-event clinical characteristics, comparator robustness and multiplicity correction. Results: Dermatologic adverse events were identified in 996,654 reports, including 425 CAR-T-associated cases. CAR T-cell exposure was associated with reduced adjusted reporting odds for the primary outcome (adjusted odds ratio 0.13, 95% confidence interval 0.09–0.20) and broad severe cutaneous adverse reactions (0.35, 0.23–0.52). The primary SKIN_ANY reduced-reporting pattern was consistent across all-FAERS, haematological-malignancy and active haematology-oncology comparators. HSCT/GVHD proxy co-reporting was uncommon and did not materially alter estimates. Severe dermatologic reports frequently co-mentioned CRS and serious outcomes. The tisagenlecleucel vascular cutaneous signal was nominally significant but attenuated after excluding infection-attributable and cytopenia/bleeding-proxy reports. Conclusions: Within spontaneous reporting systems, CAR T-cell therapy showed reduced relative reporting of dermatologic adverse events across broad, phenotype-specific and product-level analyses. These results should be interpreted as differences in reporting behaviour, not as evidence of reduced true clinical incidence or lower patient-level risk. Early severe cutaneous reports frequently overlapped with cytokine release syndrome, while infection, cytopenia/bleeding proxies and supportive-care drugs were important alternative explanations for selected cutaneous signals. Full article

Background/Objectives: Outcomes after CD19-directed chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory (R/R) aggressive large B-cell lymphoma (aLBCL) remain heterogeneous. Tumor genomic biomarkers, such as TP53 alteration, MYC/BCL2/BCL6 rearrangement-defined double-hit or triple-hit lymphoma (DHL/THL), cell of origin (COO), and complex karyotype, are established or candidate prognostic factors in conventionally treated lymphoma, but their relevance after CAR T-cell therapy is uncertain. We conducted a systematic review with exploratory meta-analysis of biomarker-stratified outcomes after CD19 CAR T-cell therapy in aLBCL. Methods: We searched MEDLINE, Embase, and Web of Science/BIOSIS (April 2026), with targeted PubMed citation lookup during full-text retrieval (PROSPERO CRD420261350514). Eligible studies enrolled adults with R/R disease treated with protocol-eligible CD19 CAR T-cell therapy and reported prespecified tumor genomic biomarkers with stratified outcomes. Random-effects models, using restricted maximum-likelihood estimation with Hartung–Knapp–Sidik–Jonkman (HKSJ) adjustment, were fitted when at least three comparable, non-overlapping studies provided extractable data. Results: After duplicate removal, 182 records were screened, 37 were assessed for eligibility, and 26 studies were included in the qualitative synthesis; 10 contributed to 4 pooled analyses. DHL/THL-positive disease was associated with worse unadjusted overall survival (OS) (hazard ratio [HR] 1.52; 95% confidence interval [CI], 1.21–1.89; 95% prediction interval (PI), 0.56–4.08), and non-Germinal center B-cell-like (GCB)/ABC COO with worse adjusted progression-free survival (PFS) (HR 1.44; 95% CI, 1.04–2.00; 95% PI, 0.86–2.43). The complete-response analyses for TP53 alteration (OR 1.30; 95% CI, 0.01–156.60) and COO (OR 1.27; 95% CI, 0.24–6.61) were statistically uninformative. No study permitted evaluation of complex karyotypes. Conclusions: Biomarker-stratified evidence after CD19 CAR T-cell therapy is sparse and inconsistently reported. DHL/THL status and non-GCB/activated B-cell-like (ABC) COO showed exploratory survival signals, whereas the TP53 and COO complete-response analyses were uninformative. These biomarkers remain hypothesis-generating rather than validated predictors of CAR T-cell outcome, and standardized, prospective biomarker-stratified reporting is needed. Full article

Background: Chimeric antigen receptor T-cell (CAR-T) therapies have transformed the treatment of haematologic malignancies, yet their adverse event (AE) profiles across all approved agents have not been consolidated using a pharmacovigilance methodology in a single comparative analysis. Methods: Using the FDA Adverse Events Reporting System (FAERS) and OpenVigil 2.1, disproportionality analyses for all six FDA-approved CAR-T therapies were performed, stratified by target antigen: anti-CD19 agents (axicabtagene ciloleucel, tisagenlecleucel, lisocabtagene maraleucel, brexucabtagene autoleucel) and anti-BCMA agents (idecabtagene vicleucel, ciltacabtagene autoleucel). For each of the 25 most frequently reported AEs per agent, the report event counts, reporting odds ratio (ROR) with 95% confidence interval, proportional reporting ratio (PRR), and chi-squared statistic were calculated. Results: A total of 36,567 AEs were identified across all six agents. Cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were the most frequent and most disproportionate AEs across all six therapies, with RORs exceeding 240 in every agent. Idecabtagene vicleucel had the highest ROR for cytokine release syndrome among all agents (ROR 1934.6), while brexucabtagene autoleucel had the highest ROR for immune effector cell-associated neurotoxicity syndrome (ROR 2089.6). Ciltacabtagene autoleucel exhibited a unique neurological toxicity profile, cranial nerve paralysis (ROR 3167.6, PRR 3055.0, chi² 199,190), parkinsonism (ROR 145.5, PRR 136.6, chi² 24,840), Bell’s palsy (ROR 380.4, PRR 370.3), and facial paralysis (ROR 72.7), consistent with the late neurotoxicity syndrome previously characterized, and absent from other agents’ top 25 AE lists. Brexucabtagene autoleucel demonstrated secondary malignancy signals including squamous cell carcinoma of skin (ROR 308.2) and myelodysplastic syndrome (ROR 97.9). Tisagenlecleucel showed the highest hypogammaglobulinemia signal among all agents (ROR 614.1, PRR 536.5, chi² 144,832) alongside a broad pancytopenia profile. Hemophagocytic lymphohistiocytosis was a significant finding with ciltacabtagene autoleucel (ROR 71.0) and brexucabtagene autoleucel (ROR 57.8). Conclusions: CAR-T therapies share class-wide toxicities in cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, but exhibit clinically important drug-specific and target-class-specific AE profiles. This consolidated FAERS-based analysis corroborates and extends prior pharmacovigilance work by providing direct cross-agent comparisons, and supports the use of agent-tailored monitoring strategies, particularly for the distinctive late neurological toxicity associated with ciltacabtagene autoleucel. Full article

Autoimmune endocrine diseases constitute a group of disorders characterized by immune-mediated destruction or dysfunction of hormone-producing glands. The pathogenesis of these diseases reflects a breakdown of immune tolerance in which regulatory T cells (Tregs) play a key role. The transcription factor forkhead box P3 (FOXP3) is a master regulator of Treg differentiation and suppressive function. Also, it is central to maintaining self-tolerance. Genetic mutations in FOXP3, including those responsible for immune dysregulation, polyendocrinopathy, enteropathy X-linked (IPEX) syndrome, highlight the critical role of FOXP3 in endocrine immune tolerance. Emerging evidence suggests that autoimmune endocrine disorders may reflect organ-specific destabilization of FOXP3 expression rather than complete Treg deficiency. The reversibility or irreversible loss of FOXP3 gene expression represents a key determinant of Treg plasticity and the persistence of autoimmune inflammation. This review proposes an integrated genetic–epigenetic model of FOXP3 instability and examines how the endocrine microenvironment shapes Treg plasticity. Genetic or epigenetic alterations affecting FOXP3 expression can impair Treg activity and precipitate endocrine organ-specific autoimmunity. Epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNA-mediated regulation that modulate FOXP3 transcriptional activity are discussed. From a translational perspective, the potential of FOXP3 as a biomarker for endocrine disease susceptibility and progression was summarized. Furthermore, therapeutic strategies employed for expanding or engineering functional FOXP3⁺ Tregs using antigen-specific vaccines, chimeric antigen receptors (CAR)-Tregs, gene therapy, or low-dose interleukin-2 (IL-2) were described. Full article

B-cell maturation antigen (BCMA), G protein-coupled receptor class C group 5 member D (GPRC5D)-directed immunotherapies, chimeric antigen receptor T-cell (CAR-T) products, bispecific T-cell engagers (BsAbs), and antibody–drug conjugates (ADCs), have transformed the management of MM. Their adoption is now extending beyond tertiary centers following FDA modifications for CAR-T safety and the rapid uptake of off-the-shelf bispecifics suitable for community delivery. Clinicians outside specialist hubs must therefore be conversant with the full toxicity spectrum, including rare but high-consequence events, both for informed consent and for the work-up of post-therapy complications. In this narrative review, we report on the published literature around toxicities of approved and investigational BCMA- and GPRC5D-directed therapies, drawing on pivotal trial data, real-world cohorts, pharmacovigilance studies, and consensus management recommendations, with emphasis on practical recognition and risk mitigation. This review presents toxicities by a temporal pattern including acute (CRS, ICANS, infection, ocular, mucocutaneous), subacute (cranial nerve palsies, parkinsonism, myelitis, peripheral neuropathies IEC-associated enterocolitis and cardiovascular events), and long-term (prolonged cytopenias, second primary malignancies). We discuss validated risk stratification tools, such as the CAR-HEMATOTOX score, EASIX index, and multidisciplinary geriatric assessment, which predicts severe ICANS, infection, and resource utilization, supporting individualized pre-treatment planning. Safe delivery of immune therapies in community settings requires infrastructure for acute critical care, neurology, ophthalmology, infectious disease and long-term surveillance, but is achievable when paired with validated risk stratification and clear referral pathways. Full article

CD19-directed chimeric antigen receptor (CAR) T-cell therapy has fundamentally transformed the treatment landscape for relapsed and refractory B-cell malignancies, yet antigen escape remains a persistent therapeutic challenge that limits long-term remission durability. While antigen loss is typically considered a somatic event acquired during tumor evolution under therapeutic selective pressure, germline CD19 polymorphisms could theoretically influence CAR-binding kinetics, alter epitope presentation, and modulate therapeutic outcomes in ways that remain largely not characterized. Unfortunately, Middle Eastern populations are underrepresented in pharmacogenomic databases and CAR-T clinical trials, creating a knowledge gap that may perpetuate global health disparities in access to precision immunotherapy. We analyzed publicly available whole-exome sequencing data from 1196 individuals of Arab origin to comprehensively characterize CD19 variants with potential relevance to CAR T-cell immunotherapy. The L174V (rs2904880) variant stood out, and showed the Valine/Valine (V/V) genotype frequency was 65.3%, corresponding to a V174 allelic frequency of 76.6%, while the minor allele, L174, has a frequency of 23.4%. The missense mutation (c.520C > G) responsible for this variant results in a leucine-to-valine (L174V) substitution at position 174 of the CD19 protein, relative to the reference genome. The cohort genotypes (CC, CG, and GG) exhibited a significant deviation from Hardy–Weinberg equilibrium (p < 0.00001). While this deviation is consistent with the high consanguinity rates (25–60%) amongst Arab populations, it remains not fully explained, and may be attributed to population structure, relatedness, or technical factors. We further emphasize that our computational analysis cannot establish any direct clinical or functional impact due to this variant, and therefore we refrain from suggesting any specific actions at the current time. In light of these findings, we hypothesize that the distinctive genetic architecture of consanguineous populations should not be viewed as a confounding variable. Instead, it presents a unique opportunity to investigate the clinical relevance of germline variation in the context of precision oncology, particularly at therapy-relevant loci, pending functional validation. Full article

Clear cell renal cell carcinoma (ccRCC) accounts for approximately 75% of renal cell carcinomas and is defined by near-universal VHL inactivation, leading to constitutive HIF stabilisation, metabolic reprogramming, and an immunologically distinct tumour microenvironment (TME). Although ccRCC is characterised by abundant immune infiltration, this paradoxically correlates with poor prognosis, reflecting a TME that imposes interconnected physical, immunological, and metabolic barriers to effective immunotherapy. Chimeric antigen receptor (CAR)-based therapies have revolutionised the treatment of haematological malignancies, but their translation to ccRCC has encountered substantial hurdles. The first-in-human trial targeting carbonic anhydrase IX (CAIX) was limited by on-target off-tumour toxicity and CAR immunogenicity—lessons that fundamentally reshaped the field. CD70 has since emerged as the dominant clinical target, expressed in over 80% of ccRCCs with a highly restricted normal tissue distribution. The phase I COBALT-RCC trial of CTX130, an allogeneic CRISPR-Cas9-edited CD70-directed CAR-T cell product, provided formal proof of concept, achieving disease control in 81.3% of heavily pretreated patients and a durable complete response now exceeding three years—the first such sustained remission reported for any CAR-T cell product in a solid malignancy. Nevertheless, the low frequency of durable responses and universal loss of CAR-T cell persistence by day 28 underscore that major barriers remain. Beyond CD70, the field has diversified across multiple platforms, including CAR–natural killer (NK) cells, CAR–natural killer T (NKT) cells, and CAR–macrophages, each offering distinct biological advantages. This review synthesises current knowledge of the ccRCC TME, the preclinical landscape of CAR-based therapies, and emerging clinical evidence from more than 30 registered trials. We discuss target antigens; engineering strategies to overcome TME barriers, including cytokine armouring, chemokine receptor co-expression, switch receptors, and metabolic reprogramming; and rational combination approaches. We argue that the convergence of optimised target selection, cellular engineering, combination strategies, and biomarker-driven trial design may ultimately improve outcomes for patients with ccRCC. However, achieving a cure remains an aspirational goal, and significant barriers must first be overcome. Full article

Background: BCMA-targeted Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized the treatment of Relapsed/Refractory Multiple Myeloma (RRMM). However, the disease is not curable and progression after CAR T-cell treatment remains a challenge. Clonal hematopoiesis, specifically mutations in the DNA damage response gene PPM1D, has been linked to therapy resistance and inferior survival in lymphoma patients undergoing cellular therapy. The impact of PPM1D mutations on MM patient outcome after CAR T-cell therapy remains undefined. Methods: We conducted a retrospective single-center study of 83 patients with RRMM patients treated with idecabtagene vicleucel or ciltacabtagene autoleucel between 2022 and 2025. Next-generation sequencing was performed on peripheral blood mononuclear cells collected prior to CAR T-cell infusion to identify PPM1D exon 6 mutations (variant allele frequency > 0.01). We analyzed associations between mutational status, clinical characteristics, toxicity, and survival. Results: PPM1D mutations were detected in 14.5% (12/83) of patients. PPM1D-mutated patients had fewer prior autologous stem cell transplantation compared to wild-type patients (50% vs. 82%, p = 0.02) and presented more advanced disease burden and adverse prognostic features (R-ISS stage III 58% vs. 20%, p = 0.05). Notably, PPM1D status did not impact initial efficacy; complete remission rates were comparable between groups (67% vs. 69%). However, PPM1D mutations were significantly associated with inferior progression-free survival (PFS) (median PFS: 6 months vs. 16 months, p = 0.04). Regarding toxicity, the mutated subgroup exhibited significantly higher rates of grade ≥2 cytokine release syndrome and a trend toward increased neurotoxicity (25% vs. 7%). Conclusions: PPM1D clonal hematopoiesis is frequent in RRMM and despite deep initial responses, patients harboring PPM1D mutations face a significantly higher risk of early relapse. PPM1D mutations may serve as a biomarker for poor durability of response and should be further evaluated in larger, prospective trials. Full article

Background/Objectives: Lisocabtagene maraleucel (liso-cel) is a CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy approved for relapsed or refractory large B-cell lymphoma (R/R LBCL). However, most published meta-analyses of CAR-T therapy in LBCL pool data across products, limiting product-specific interpretation. Methods: We conducted a systematic review and meta-analysis of clinical trials and retrospective real-world studies evaluating liso-cel monotherapy in R/R LBCL. The primary endpoint was the overall response rate (ORR). Secondary endpoints included complete response (CR), incidence of grade ≥ 3 adverse events, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), overall mortality rate (OMR), disease progression-related mortality, and adverse event-related mortality. Pooled proportions were estimated using random-effects models. Results: Eleven studies including 1206 patients were analyzed, comprising five clinical trials and six real-world retrospective cohorts. The pooled ORR was 78%, and the pooled CR rate was 60%. The pooled OMR was 38%, with a disease progression-related mortality of 28% and an adverse event-related mortality of 4%. Severe (grade ≥ 3) CRS and ICANS occurred in 2% and 8%, respectively. Severe (grade ≥ 3) hematologic toxicities were frequent, particularly neutropenia, thrombocytopenia, and anemia. Conclusions: Liso-cel monotherapy demonstrated high pooled response rates and low pooled incidences of severe CRS and ICANS across clinical trials and real-world settings in R/R LBCL. Severe ICANS, although uncommon, remains clinically meaningful, and severe hematologic toxicities were frequent and warrant careful monitoring and supportive care. These findings provide product-specific benchmarks for liso-cel in R/R LBCL. Full article

Background/Objectives: Therapeutic options for patients with relapsed and refractory multiple myeloma (RRMM) have advanced substantially in recent years. In particular, T-cell-engaging therapies, including chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies (bsAbs), have emerged as highly effective treatment modalities. However, data on predictive biomarkers for response to these therapies remain limited. Patients currently receiving T-cell-engaging therapies are typically heavily pretreated and frequently exhibit clonal hematopoiesis. Clonal hematopoiesis, especially involving PPM1D mutations, may adversely affect the efficacy of T-cell-engaging therapies. Methods: We conducted a retrospective, single-center study including 27 patients with RRMM who were treated with bsAbs (teclistamab, elranatamab, or talquetamab) between June 2022 and September 2025 and for whom genetic material was available before bsAB treatment. We evaluated the impact of PPM1D mutations on treatment response, progression-free survival (PFS), and overall survival (OS). Results: The prevalence of PPM1D mutations in our cohort was 27%. Compared with patients without PPM1D mutations, mutation carriers showed a trend toward less deep remissions and demonstrated significantly inferior 6-month PFS (43% vs. 85%, p = 0.0272) and 6-month OS (57% vs. 90%, p = 0.0473). Conclusions: These findings suggest that PPM1D mutations may represent a promising biomarker in patients with RRMM treated with bsAbs. Larger, prospective studies are warranted to validate and further elucidate these observations. Full article

While chimeric antigen receptor (CAR)-T-cell therapies have shown significant effectiveness in hematological malignancies, their efficacy in solid tumors remains limited by the hostile tumor microenvironment (TME) and antigen heterogeneity. Recently, CAR-Macrophage (CAR-M) therapy has emerged as a paradigm-shifting approach, leveraging the innate capability of macrophages to deeply infiltrate tumors and their plasticity to reverse immunosuppression. Unlike T cells, CAR-Ms not only mediate direct phagocytosis but also initiate epitope spreading, effectively bridging innate and adaptive immunity. This review critically examines the trajectory of CAR-M therapy from biological rationale to clinical reality. We dissect the engineering evolution of CAR constructs, arguing for macrophage-specific signaling domains (e.g., FcRγ, Megf10) over traditional T-cell designs. Crucially, we address the major bottlenecks in clinical translation, including the manufacturing challenges of non-expanding primary macrophages and the emerging shift toward induced pluripotent stem cell (iPSC)-derived platforms. Furthermore, we evaluate current clinical trial landscapes and discuss next-generation strategies such as in vivo programming via lipid nanoparticles (LNPs) and synthetic logic-gating to enhance safety. Ultimately, overcoming manufacturing constraints and optimizing delivery systems will be pivotal for CAR-M to evolve from a niche therapy into a standard-of-care modality for solid tumors. Full article

Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in hematologic malignancies, and its development is being actively pursued across a broad range of cancer types. However, current CAR-T cell therapies rely on ex vivo engineering, which presents significant logistical, temporal, and biological limitations. In vivo CAR-T cell engineering is emerging as a new paradigm that may overcome these challenges by enabling the direct reprogramming of immune cells within the patient through the administration of CAR-encoding vectors. This approach represents an off-the-shelf form of autologous immune therapy. Advances in viral engineering and nanotechnology have enabled the development of diverse CAR delivery platforms that not only deliver CAR constructs but also facilitate the delivery of gene-editing components, such as Cas9, allowing for more sophisticated in vivo genetic modifications. Some of these approaches have already entered clinical evaluation and have shown promising early results in hematologic malignancies, with clinical trials in solid tumors now underway. However, the application of in vivo-engineered CAR-T cell therapies to malignant glioma remains largely unexplored, reflecting challenges distinct from those encountered in hematologic malignancies. In this review, we discuss these challenges and potential strategies to address them, while highlighting recent progress in in vivo CAR-T cell engineering. Full article

Medulloblastoma is one of the most prevalent pediatric brain tumors. Currently, existing therapies for this devastating type of cancer can only prolong survival time with severe side-effects and relapse. These therapies are not curative for almost a third of treated patients, while most survivors are condemned to a poor quality of life. The addition of immune checkpoint inhibitors (ICIs) to immune therapy has given some hope to those suffering from this type of cancer. Although ICIs provide a valuable contribution to immunotherapy, the exploitation of immune checkpoint inhibition within existing therapeutic strategies to cure Medulloblastoma remains understudied. However, the identification of the main molecular subgroups of medulloblastoma is considered one of the success stories of oncology. This advancement in molecular profiling of MB paved the way to subgroup-directed clinical trials, which may lead to efficacious immune-targeted therapy. However, this relatively new development is still hampered by a substantial biological heterogeneity of the disease and the absence of a full understanding of the various mechanisms behind its resistance to existing therapeutic modalities. The inclusion of chimeric antigen receptor (CAR) T and CAR NK cell therapy within various therapeutic strategies and ongoing clinical trials has given fresh hope those suffering from this fatal disease. However, ongoing clinical trials suggest that this highly promising therapy can be impaired by a number of serious limitations, including cytokine release syndrome, Graft-versus-host disease, the scarcity of target antigens, and severe adverse events. Some of the ongoing clinical trials also suggest that CAR NK is less prone to some of these limitations. This review also highlights the contribution of mass spectrometry-based proteomics, and the increasing role of liquid biopsy rather than tissue biopsy. Full article

Chimeric antigen receptor (CAR) T-cell therapy is a new standard of care for patients with diffuse large B-cell lymphoma (DLBCL); however, studies including healthcare resource utilization (HRU) during routine care are lacking. Accordingly, a population-based study was conducted using linked administrative databases from Ontario, Canada. Patients with DLBCL that failed ≥2 lines of systemic therapy were included. Cox proportional hazard models estimated associations between covariates and overall survival (OS). Logistic, binomial and Poisson regression explored associations between covariates with toxicity and HRU. We identified 308 patients enrolled to receive CAR T-cell therapy of which 255 patients received CAR T-cells (mean age 59 years; 39% female). From the date of CAR T-cell infusion, the median OS was 25.0 months (95% CI, 21.6–28.1 months). Cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome data were available for 155 patients and were reported in 135 (87.1%) and 42 (27.1%) patients, respectively. Of those that received CAR-T cells, 172 patients (67%) were hospitalized with a median length of stay of 5 days (IQR, 0–20) and 243 (95%) had an emergency department visit without hospitalization. Our prospective population-based study demonstrates comparable efficacy and safety of CAR T-cell therapy in the real-world to the pivotal trials and highlights this as an efficacious and relatively safe treatment option for patients with DLBCL in routine clinical care. Full article