Monitoring T Cells Responses Mounted by Therapeutic Cancer Vaccines

Abstract

With the regulatory approval of Provenge and Talimogene laherparepvec (T-VEC) for the treatment of metastatic prostate cancer and advanced melanoma respectively, and other promising clinical trials outcomes, cancer vaccine is gaining prominence as a cancer therapeutic agent. Cancer vaccine works to induce T cell priming, expansion, and infiltration resulting in antigen-specific cytotoxicity. Such an approach that can drive cytotoxicity within the tumor could complement the success of checkpoint inhibitors as tumors shown to have high immune cell infiltration are those that would respond well to these antibodies. With the advancements in cancer vaccine, methods to monitor and understand how cancer vaccines modify the immune milieu is under rapid development. This includes using ELISpot and intracellular staining to detect cytokine secretion by activated T cells; tetramer and CyTOF to quantitate the level of antigen specific T cells; proliferation and cell killing assay to detect the expansion of T cell and specific killing activity. More recently, T cell profiling has provided unprecedented detail on immune cell subsets and providing clues to the mechanism involved in immune activation. Here, we reviewed cancer vaccines currently in clinical trials and highlight available techniques in monitoring the clinical response in patients.

Cellular Immunity Is Critical for Assessing COVID-19 Vaccine Effectiveness in Immunocompromised Individuals

“…In contrast, measurements of cellular immunity require living peripheral blood mononuclear cell (PBMC) samples which have more complex handling requirements. These logistical deterrents were not insurmountable as cellular immunity measurements are commonplace in a variety of clinical trials, including examples in CAR-T ( 100 ), immunomodulatory oncology treatments ( 43 , 101 ), HIV ( 102 ), novel flu vaccination ( 103 , 104 ), minimal residual disease (MRD) assessment ( 105 , 106 ) and others ( 107 , 108 ). However, it should be noted that cellular immunity assays are typically limited to early stage and smaller clinical trials.…”

Lipid- and Polymer-Based Nanocarrier Platforms for Cancer Vaccine Delivery

“…4 Another approach is the use of cancer vaccines in combination with checkpoint inhibitors which may function synergistically and complement the success of checkpoint inhibitors, as tumors shown to have high infiltering lymphocytes are those that would respond well to these antibodies. 5 The role of cancer vaccines is to induce T cell activation and expansion and effector T cell infiltration, priming patients for treatments with immune checkpoint inhibitors by enhancing antigen-specific cytotoxicity and immune checkpoint signals. 6 As summarized in Figure 1, cancer vaccines are designed to elicit an immune response in the tumor tissue that effectively leads to destruction of tumor cells.…”

“…For example, checkpoint inhibitors have been used in combination with chemotherapy and other treatments to ensure better clinical outcomes . Another approach is the use of cancer vaccines in combination with checkpoint inhibitors which may function synergistically and complement the success of checkpoint inhibitors, as tumors shown to have high infiltering lymphocytes are those that would respond well to these antibodies …”

The need for more holistic immune profiling in next-generation SARS-CoV-2 vaccine trials

“…These logistical challenges are not insurmountable. Measurements of cellular immunity are implemented routinely in clinical trials for a variety of indications ( 39 – 44 ). Profiling of immunological cells at trial screening is absolutely required for CAR-T programs to ensure proper T cell depletion pre-treatment, and proper CAR-T infusion post-treatment ( 45 ).…”

“…Profiling of immunological cells at trial screening is absolutely required for CAR-T programs to ensure proper T cell depletion pre-treatment, and proper CAR-T infusion post-treatment ( 45 ). Immunological profiling at trial screening is also relatively commonplace for companion diagnostics in the oncology field ( 39 ), and evaluation of vaccine efficiency in a highly pre-exposed population is routine in influenza vaccine trials. Recently, results from a phase I clinical trial evaluating a T cell-stimulating peptide vaccine were published ( 46 ).…”