Current modalities in cancer immunotherapy: Immunomodulatory antibodies, CARs and vaccines

Abstract

Successes of immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cell therapy in curing patients with otherwise lethal cancers have validated immunotherapy as a treatment for cancer and have inspired excitement for its broader potential. Most promising is the ability of each approach to eliminate bulky and advanced-stage cancers and to achieve durable cures. Despite this success, to date only a subset of cancer patients and a limited number of cancer types respond to these therapies. A major goal now is to expand the types of cancer and number of patients who can be successfully treated. To this end a multitude of immunotherapies are being tested clinically in new combinations, and many new immunomodulatory antibodies and CARs are in development. A third major immunotherapeutic approach with renewed interest is cancer vaccines. While over 20 years of therapeutic cancer vaccine trials have met with limited success, these studies have laid the groundwork for the use of therapeutic vaccines in combination with other immunotherapies or alone as prophylactic cancer vaccines. Prophylactic vaccines are now poised to revolutionize cancer prevention as they have done for the prevention of infectious diseases. In this review we examine three major cancer immunotherapy modalities: immunomodulatory antibodies, CAR T cell therapy and vaccines. For each we describe the current state of the art and outline major challenges and research directions forward.

Ovarian cancer: Current status and strategies for improving therapeutic outcomes

“…Use of cancer vaccines is another approach to bring about immune activation. T‐cell responses were stimulated by activating the antigen‐presenting cells . More recently, 11 heavily treated patients with platinum‐resistant OC (PROC) have been treated with GL‐ONC1 on a phase Ib protocol [NCT02759588].…”

“…T-cell responses were stimulated by activating the antigen-presenting cells. 84 More recently, 11 heavily treated patients with platinum-resistant OC (PROC) have been treated with GL-ONC1 on a phase Ib protocol [NCT02759588]. GL-ONC1 is a modified vaccinia virus developed by Genelux Corporation (San Diego, CA) that causes tumor cell oncolysis, immune activation through release of oncoproteins, presentation of both foreign and tumor antigens by dendritic cells, and durable anti-cancer T cell tumor-specific memory.…”

Turbocharging vaccines: emerging adjuvants for dendritic cell based therapeutic cancer vaccines

“…Vaccinating against non-infectious tumors is entirely reliant on the availability of early tumor biomarkers. Several such antigens have been suggested but have yet to fare through clinical trials [65]. In the future, powered by new technologies, early and unique markers of tumorigenisis will be discovered and together with existing therapies shall enable preventive cancer vaccination.…”

Post-translational covalent assembly of CAR and synNotch receptors for programmable antigen targeting

“…Adoptively transferred CAR T cells targeting the B cell antigen CD19 are now FDA-approved and have been highly successful in treating refractory acute lymphoblastic leukemia [5][6][7] . Creating CARs against additional targets to treat other types of cancer and immune-related diseases is a major research focus 8,9 . Another class of highly versatile antigen receptors are synthetic Notch, "synNotch" receptors which consist of an antigen binding domain, the Notch core protein from the Notch/Delta signaling pathway, and a transcription factor [10][11][12] .…”