Abstract: Targeted delivery of chemotherapeutics and diagnostic agents conjugated to carrier ligands has made significant progress in recent years, both in regards to the structural design of the conjugates and their biological effectiveness. The goal of targeting specific cell surface receptors through structural compatibility has encouraged the use of peptides as highly specific carriers as short peptides are usually non-antigenic, are structurally simple and synthetically diverse. Recent years have seen many developments in the field of peptide based drug conjugates (PDCs), particularly for cancer therapy, as their use aims to bypass off-target side-effects, reducing the morbidity common to conventional chemotherapy. However, no PDCs have as yet obtained regulatory approval. In this review, we describe the evolution of the peptide-based strategy for targeted delivery of chemotherapeutics and discuss recent innovations in the arena that should lead in the near future to their clinical application.
Abstract: Epithelial ovarian cancer (EOC) is one important cause of gynecologic cancer-related death. Currently, the mainstay of ovarian cancer treatment consists of cytoreductive surgery and platinum-based chemotherapy (introduced 30 years ago) but, as the disease is usually diagnosed at an advanced stage, its prognosis remains very poor. Clearly, there is a critical need for new treatment options, and immunotherapy is one attractive alternative. Prophylactic vaccines for prevention of infectious diseases have led to major achievements, yet therapeutic cancer vaccines have shown consistently low efficacy in the past. However, as they are associated with minimal side effects or invasive procedures, efforts directed to improve their efficacy are being deployed, with Dendritic Cell (DC) vaccination strategies standing as one of the more promising options. On the other hand, recent advances in our understanding of immunological mechanisms have led to the development of successful strategies for the treatment of different cancers, such as immune checkpoint blockade strategies. Combining these strategies with DC vaccination approaches and introducing novel combinatorial designs must also be considered and evaluated. In this review, we will analyze past vaccination methods used in ovarian cancer, and we will provide different suggestions aiming to improve their efficacy in future trials.
Abstract: Gene transfer technology and its application to human gene therapy greatly expanded in the last decade. One area of investigation that appears particularly promising is the transfer of new genetic material into T cells for the potential treatment of cancer. Herein, we describe several core technologies that now yield high-efficiency gene transfer into primary human T cells. These gene transfer techniques include viral-based gene transfer methods based on modified Retroviridae and non-viral methods such as DNA-based transposons and direct transfer of mRNA by electroporation. Where specific examples are cited, we emphasize the transfer of chimeric antigen receptors (CARs) to T cells, which permits engineered T cells to recognize potential tumor antigens.
Abstract: Stem cell gene therapy approaches for Human Immunodeficiency Virus (HIV) infection have been explored in clinical trials and several anti-HIV genes delivered by retroviral vectors were shown to block HIV replication. However, gammaretroviral and lentiviral based retroviral vectors have limitations for delivery of anti-HIV genes into hematopoietic stem cells (HSC). Foamy virus vectors have several advantages including efficient delivery of transgenes into HSC in large animal models, and a potentially safer integration profile. This review focuses on novel anti-HIV transgenes and the potential of foamy virus vectors for HSC gene therapy of HIV.
Abstract: Innate lymphoid cells (ILCs) are a group of immune cells of the lymphoid lineage that do not possess antigen specificity. The group includes natural killer (NK) cells, lymphoid tissue inducer (LTi) cells and the recently identified ILC1s, ILC2s and ILC3s. Although the role of NK cells in the context of cancer has been well established, the involvement of other ILC subsets in cancer progression and resistance is just emerging. Here, we review the literature on the role of the different ILC subsets in tumor immunity and discuss its implications for cancer treatment and monitoring.
Abstract: Anti-cancer immunotherapy is emerging from a nadir and demonstrating tangible benefits to patients. A variety of approaches are now employed. We are invoking antigen (Ag)-specific responses through direct injections of recombinant lentivectors (LVs) that encode sequences for tumor-associated antigens into multiple lymph nodes to optimize immune presentation/stimulation. Here we first demonstrate the effectiveness and antigen-specificity of this approach in mice challenged with prostate-specific antigen (PSA)-expressing tumor cells. Next we tested the safety and efficacy of this approach in two cohorts of rhesus macaques as a prelude to a clinical trial application. Our vector encodes the cDNA for rhesus macaque PSA and a rhesus macaque cell surface marker to facilitate vector titering and tracking. We utilized two independent injection schemas demarcated by the timing of LV administration. In both cohorts we observed marked tissue-specific responses as measured by clinical evaluations and magnetic resonance imaging of the prostate gland. Tissue-specific responses were sustained for up to six months—the end-point of the study. Control animals immunized against an irrelevant Ag were unaffected. We did not observe vector spread in test or control animals or perturbations of systemic immune parameters. This approach thus offers an “off-the-shelf” anti-cancer vaccine that could be made at large scale and injected into patients—even on an out-patient basis.