Immunotherapeutic Agents for Intratumoral Immunotherapy
Abstract
:1. Introduction
1.1. Systemic Cancer Immunotherapy
1.2. Locoregional Intratumoral Immunotherapy
2. Classes of Intratumoral Immunotherapeutic Agents in Preclinical and Clinical Studies
2.1. Small and Macromolecules
2.2. Peptides and Proteins
2.3. Nucleic Acid-Based Gene Products
2.4. Microbes
2.4.1. Viruses
2.4.2. Bacteria
2.5. Cells
3. Clinical Challenges for Intratumoral Immunotherapy with Immune Modulators
3.1. Feasibility of Intratumoral Injection Tumor Size and Location Limits
3.2. Intratumoral Immunotherapy Pharmacology and Toxicology
3.3. Clinical Outcome Assessment and Application
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Class | Agent | Target Tumor Type | Development Stage | Main Result | Reference |
---|---|---|---|---|---|
Small and macromolecule | Imiquimod | Mesothelioma | Preclinical murine model | 30% Complete resolution | [17] |
MIW815 (ADU-S100) | Solid tumors or lymphomas | Phase Ib | 10.4% Overall response rate | [18] | |
G100 | Lymphoma | Phase I/II | 33.3% Overall response rate | [19] | |
CpG oligodeoxynucleotide | Colon; Breast | Preclinical murine model | Survival benefit | [20] | |
Vidutolimod | Lung | Phase Ib | 15.4% to 25.0% Response rate | [21] | |
α-gal glycolipid | Advanced solid tumors | Phase I | No DLT | [22] | |
Peptides and Proteins | LTX-315 (ruxotemitide) | Advanced solid tumors | Phase I | Immune-mediated anticancer activity | [23] |
IL-2 | Melanoma | Phase II | 36.7% Overall response rate | [24] | |
IFNα-2a | Basal cell carcinoma | Clinical study | 55% Complete remission | [25] | |
IFNα-2b | Basal cell carcinoma | Clinical study | 80% Cured | [26] | |
IFNγ | Melanoma | Clinical study | Enhance T-cell infiltration and mediated tumor control | [27] | |
GM-CSF | Melanoma | Phase I | 23% Partial regression | [28] | |
L19-IL2 and L19-TNF | Melanoma | Phase II | 20 Efficacy-evaluable patients, 32 melanoma lesions complete responses | [29] | |
Anti-CTLA4 | Glioblastoma | Phase I | 34% Two-year overall survival rate | [30] | |
Anti-PD-1 | Basal cell carcinoma | Phase I | 45% Tumor reduction ≥25% | [31] | |
Anti-CD40 | Breast; melanoma; advanced solid tumors | Phase I | Clinical activity observed | [32,33] | |
Trastuzumab-vc-MMAE | Gastric carcinoma | Preclinical murine model | Increased antitumor activity | [34] | |
Nucleic acid-based gene products | tavokinogene telseplasmid | Melanoma | Phase II | 35.7–41% Overall response rate | [35,36] |
MEDI1191 | Advanced solid tumors | Phase I | Preliminary antitumor activity | [37] | |
mRNA-2752 | Advanced solid tumors | Phase I | 5.8% Overall response rate | [38] | |
SAR441000 | Advanced solid tumors | Phase I | Generally, well tolerated | [39] | |
TriMix mRNA | Lymphoma; mastocytoma; lung | Preclinical murine model | Delay the growth of established tumors | [40] | |
Circular mRNA | Lung; melanoma; colon | Preclinical murine model | Tumor repression | [41] | |
Viruses | Talimogene laherparepvec | Melanoma (only FDA-approved indication) | Phase III | 31.5% Overall response rate | [42] |
Talimogene laherparepvec | Breast; liver | Phase II | 31.5–52% Overall response rate | [43,44] | |
CAVATAK | Melanoma | Phase II | 28.1% Overall response rate | [45] | |
Hf10 | Breast; melanoma; pancreatic; | Phase I; phase II | 25–41% Overall response rate | [46,47,48] | |
Pexastimogene devacirepvec | Liver | Phase III | Fail to improve survival | [49,50,51] | |
Teserpaturev | Glioblastoma | Phase II | 84.2% One-year survival rate | [52] | |
Tasadenoturev | Glioma | Phase I | 20% Patients survived >3 years | [53,54] | |
ONCOS-102 | Refractory solid tumors | Phase I | 40% Disease control | [55] | |
Reolysin | Pancreatic | Phase I | No difference in progression-free survival to chemotherapy | [56] | |
Cavatak | Melanoma | Phase II | 38.6% Progression-free survival at 6 months | [56] | |
PVSRIPO | Glioma | Phase 1 | 21% Survival at 24 months | [57] | |
Bacteria | Bacillus Calmette–Guérin | Non-muscle invasive bladder cancer (only FDA-approved indication) | Phase II | 76% Complete remission | [58] |
VNP20009 | Advanced or metastatic cancer | Phase I | Report a safe profile | [59]. | |
C. novyi-NT | Refractory solid tumors | Phase I | 41% Decrease in the size of the injected tumor | [60] | |
Cells | Autologous dendritic cells | Melanoma; breast | Clinical study | Regression of the injected tumors | [61] |
Ilixadencel | Gastrointestinal stromal tumor | Phase I | 33% Tumor responses | [62] | |
Tumor-infiltrating lymphocytes | Melanoma | Clinical study | Tumor regression | [63] | |
Erbb-targeted CAR-T | Squamous cell carcinoma | Phase I | 60% Stabilization of disease | [64] | |
C-Met-CAR-T | Breast | Phase 0 | Evoke an inflammatory response within tumors | [65] | |
Xenogeneic tissue cells | Bladder; breast; pancreatic | Preclinical murine model | Suppress tumor growth | [66,67] |
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Shyr, C.-R.; Liu, L.-C.; Chien, H.-S.; Huang, C.-P. Immunotherapeutic Agents for Intratumoral Immunotherapy. Vaccines 2023, 11, 1717. https://doi.org/10.3390/vaccines11111717
Shyr C-R, Liu L-C, Chien H-S, Huang C-P. Immunotherapeutic Agents for Intratumoral Immunotherapy. Vaccines. 2023; 11(11):1717. https://doi.org/10.3390/vaccines11111717
Chicago/Turabian StyleShyr, Chih-Rong, Lang-Chi Liu, Hui-Shan Chien, and Chi-Ping Huang. 2023. "Immunotherapeutic Agents for Intratumoral Immunotherapy" Vaccines 11, no. 11: 1717. https://doi.org/10.3390/vaccines11111717
APA StyleShyr, C.-R., Liu, L.-C., Chien, H.-S., & Huang, C.-P. (2023). Immunotherapeutic Agents for Intratumoral Immunotherapy. Vaccines, 11(11), 1717. https://doi.org/10.3390/vaccines11111717