Combining vaccines with conventional therapies for cancer

Abstract

Preclinical and clinical investigations currently underway are employing novel strategies for combining vaccines with conventional and experimental anticancer therapies. To date, the FDA has not approved a therapeutic cancer vaccine. However, the results of recent investigations suggest an increasing role for vaccines in new models of combination therapy for many types of cancer. This article reviews and discusses therapeutic cancer strategies that employ vaccines in combination with local radiation, chemotherapy, hormone therapy, and anti-CTLA-4 mAb. Preclinical studies have shown that certain anticancer agents have immune modulatory effects that result in up-regulation of surface expression of MHC molecules, tumor-associated antigens, or Fas on malignant cells, rendering them more susceptible to immune destruction. Preliminary results of clinical studies using combination strategies have demonstrated a postvaccination antigen cascade, prolonged time to disease progression, and improved overall survival. Several larger randomized trials are ongoing, and more are required to support these findings.

Combination Therapy with a Second-Generation Androgen Receptor Antagonist and a Metastasis Vaccine Improves Survival in a Spontaneous Prostate Cancer Model

“…This highlights the fact that tumor antigen must be expressed at high levels to elicit a robust and effective immune-mediated response. Additionally, mice that survived and received combination treatment with enzalutamide and Twist-vaccine for 12 months experienced antigen cascade (Supplemental Table 1), a host response not only to the antigen in the vaccine but also to other tumor antigens associated with a given tumor type (33, 43–45). …”

Androgen ablation augments prostate cancer vaccine immunogenicity only when applied after immunization

“…In an effort to improve clinical outcomes, current therapies are being combined in order to treat cancer. Androgen ablation is a standard line of treatment for advanced prostate cancer and is being accessed in clinical trials in combination with immunotherapy (40–42). Androgens have been found to transcriptionally regulate a variety of immune response genes (13–15), therefore the effects of androgen ablation on the immune response is complicated and requires closer investigation.…”

An MVA-based Vaccine Targeting the Oncofetal Antigen 5T4 in Patients Undergoing Surgical Resection of Colorectal Cancer Liver Metastases

“…Preclinical models support the rationale for combining cancer vaccines with conventional therapies, such as radiation, chemotherapy, surgery, and hormone therapy. 23 Additionally, several studies have shown that patient cohorts who receive a cancer vaccine benefit clinically from subsequent therapies, compared with control cohorts. 24 Indeed, TroVax has been tested alongside 2 different standard of care chemotherapy regimens in patients with CRC.…”