Abstract
Vaccines used to prevent infections have long been known to stimulate immune responses to cancer as illustrated by the approval of the Bacillus Calmette–Guérin (BCG) vaccine to treat bladder cancer since the 1970s. The recent approval of immunotherapies has rejuvenated this research area with reports of anti-tumor responses with existing infectious diseases vaccines used as such, either alone or in combination with immune checkpoint inhibitors. Here, we have reviewed and summarized research activities using approved vaccines to treat cancer. Data supporting a cancer therapeutic use was found for 16 vaccines. For 10 (BCG, diphtheria, tetanus, human papillomavirus, influenza, measles, pneumococcus, smallpox, typhoid and varicella-zoster), clinical trials have been conducted or are ongoing. Within the remaining 6, preclinical evidence supports further evaluation of the rotavirus, yellow fever and pertussis vaccine in carefully designed clinical trials. The mechanistic evidence for the cholera vaccine, combined with the observational data in colorectal cancer, is also supportive of clinical translation. There is limited data for the hepatitis B and mumps vaccine (without measles vaccine). Four findings are worth highlighting: the superiority of intravesical typhoid vaccine instillations over BCG in a preclinical bladder cancer model, which is now the subject of a phase I trial; the perioperative use of the influenza vaccine to limit and prevent the natural killer cell dysfunction induced by cancer surgery; objective responses following intratumoral injections of measles vaccine in cutaneous T-cell lymphoma; objective responses induced by human papillomavirus vaccine in cutaneous squamous cell carcinoma. All vaccines are intended to induce or improve an anti-tumor (immune) response. In addition to the biological and immunological mechanisms that vary between vaccines, the mode of administration and sequence with other (immuno-)therapies warrant more attention in future research.
Highlights
Drug repurposing, which seeks new medical uses of existing licensed drugs, is an active field in cancer research [1, 2]
In the colorectal cancer population, having received the cholera vaccine was associated with lower colorectal cancer mortality (HR, 0.53; 95% CI, 0.29–0.99) and all-cause mortality (HR, 0.59; 95% CI, 0.37–0.94)
Using murine models of metastasis, and surgical stress, they demonstrated that a single intramuscular dose of influenza vaccine delivered one day before surgery resulted in optimal activation of natural killer (NK) cells and a dramatic reduction in the metastatic dissemination of cancer cells to the lungs [9]
Summary
Drug repurposing, which seeks new medical uses of existing licensed drugs, is an active field in cancer research [1, 2]. With the growing immunotherapy armamentarium against multiple cancer types, massive research efforts are directed to finding new agents that will further expand the efficacy of these immunotherapies [3, 4] Another proposed strategy is to use existing drugs as add-on to. Several cancer research groups have reported that existing infectious diseases vaccines used as such, either systematically [9] or intratumorally [10,11,12] or both [13], were able to induce anti-tumor responses, alone or in combination with approved immune checkpoint inhibitors These experiments were performed in mice, with the exception of a case report [13]. Reformulation or manipulation of an existing vaccine (or drug), though possibly interesting to secure patent protection, renders the clinical development of the ‘new’ product less straightforward [14]
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