Therapeutic cancer vaccines: past, present, and future

Abstract

Therapeutic vaccines represent a viable option for active immunotherapy of cancers that aim to treat late stage disease by using a patient's own immune system. The promising results from clinical trials recently led to the approval of the first therapeutic cancer vaccine by the U.S. Food and Drug Administration. This major breakthrough not only provides a new treatment modality for cancer management but also paves the way for rationally designing and optimizing future vaccines with improved anticancer efficacy. Numerous vaccine strategies are currently being evaluated both preclinically and clinically. This review discusses therapeutic cancer vaccines from diverse platforms or targets as well as the preclinical and clinical studies employing these therapeutic vaccines. We also consider tumor-induced immune suppression that hinders the potency of therapeutic vaccines, and potential strategies to counteract these mechanisms for generating more robust and durable antitumor immune responses.

Keywords: Cancer vaccine; Immune modulator; Immunosuppression; Immunotherapy; Tumor microenvironment; Tumor-associated antigen.

Figure 1. Counteracting tumor-induced immune suppression to achieve effective cancer vaccine therapy

Active immunization with therapeutic vaccines generally targets the host DCs for effective presentation of tumor-associated antigens and subsequent priming of CD8⁺ CTLs and CD4⁺ T helper cells. These tumor-specific T effector cells together with other innate immune cells can result in inhibition or destruction of cancer cells. In the tumor microenvironment, cancer cells produce immunosuppressive soluble factors (TGF-β, IL-10, IDO, galectin and VEGF) and expand or recruit immune regulatory cells (MDSCs, Tregs and TAMs), which establish an immunosuppressive state at the tumor site. This complex molecular and cellular network attenuates vaccine-induced antitumor immune responses and promotes tumor escape from immune attack. To overcome the immune suppressive mechanisms, novel immune modulators (anti-CTLA-4 and anti-PD1 antibodies) may be used to enhance vaccine potency and restore durable antitumor immunity. Cancer vaccines can also be combined with conventional cancer treatments, such as radiotherapy and chemotherapy, to engage multivalent antitumor effects for optimized therapeutic efficacy.