A3.3 Vaccines and other strategies

Topic

Beyond checkpoint inhibitors and chimeric antigen receptor (CAR) T-cells, there is a wide spectrum of other immunotherapeutic strategies that target various points of the interaction between the tumor and the immune system; rather than focusing on a single mechanism, each of these strategies addresses a different limitation of existing therapies.

The first of these strategies involves neoantigen vaccines, which aim to activate tumor-specific T-cell clones and increase the rate at which these clones proliferate within the patient.

The second strategy involves bispecific antibodies, which physically link a T-cell to a tumor cell by binding one end of the antibody to the T-cell and the other to the tumor cell, bypassing the need for the tumor cell's antigen-presentation system to match that of the T-cell.

The third strategy involves antibody-drug conjugates, which leverage the specificity of an antibody—its ability to selectively recognize tumor cells—to deliver a chemotherapeutic agent directly to the tumor, rather than allowing the agent to circulate throughout the body without a specific target.

The fourth strategy involves oncolytic viruses, which selectively infect tumor cells and destroy them from within; in doing so, they also trigger the patient's immune response against the remainder of the tumor.

What at least the first three of these strategies have in common is that each overcomes a distinct limitation of earlier immunotherapies: neoantigen vaccines address the lack of pre-existing T-cell clones targeting the tumor—a common issue with tumors that the immune system barely recognizes; Bispecific antibodies overcome the need to expand T cells outside the patient's body—a requirement for chimeric antigen receptor (CAR) T cells—while antibody-drug conjugates surmount the barrier preventing many drugs from penetrating the tumor by using the antibody as a guidance system to target it. Oncolytic viruses, for their part, offer something different: they not only directly destroy the tumor cells they infect but also activate the patient's immune response against the rest of the tumor, combining a direct effect on the tumor and an effect on the immune system into a single immunotherapeutic strategy. Thus, each of these four immunotherapeutic strategies advances—via a different path—the same goal pursued by all immunotherapy: enabling the patient's immune system to recognize and destroy the tumor.

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