Abstract
With the spotlight on cancer immunotherapy and the expanding use of immune checkpoint inhibitors, strategies to improve the response rate and duration of current cancer immunotherapeutics are highly sought. In that sense, investigators around the globe have been putting spurs on the development of effective cancer vaccines in humans after decades of efforts that led to limited clinical success. In more than three decades of research in pursuit of targeted and personalized immunotherapy, several platforms have been incorporated into the list of cancer vaccines from live viral or bacterial agents harboring antigens to synthetic peptides with the hope of stronger and durable immune responses that will tackle cancers better. Unlike adoptive cell therapy, cancer vaccines can take advantage of using a patient’s entire immune system that can include more than engineered receptors or ligands in developing antigen-specific responses. Advances in molecular technology also secured the use of genetically modified genes or proteins of interest to enhance the chance of stronger immune responses. The formulation of vaccines to increase chances of immune recognition such as nanoparticles for peptide delivery is another area of great interest. Studies indicate that cancer vaccines alone may elicit tumor-specific cellular or humoral responses in immunologic assays and even regression or shrinkage of the cancer in select trials, but novel strategies, especially in combination with other cancer therapies, are under study and are likely to be critical to achieve and optimize reliable objective responses and survival benefit. In this review, cancer vaccine platforms with different approaches to deliver tumor antigens and boost immunity are discussed with the intention of summarizing what we know and what we need to improve in the clinical trial setting.
Highlights
Cancer vaccines have been extensively researched in both animal models and humans over the past 30 years across many different types of cancer
Hot tumors are defined as ones in which the tumor itself has induced an immune response of infiltrating T cells that are not able to function because of various checkpoints such as PD-1, CTLA-4, LAG3, TIM3, TIGIT, or other immunoregulatory mechanisms involving regulatory cells (regulatory T cells, myeloid-derived suppressor cells (MDSCs), M2 macrophages, regulatory natural killer (NK) T cells, and so on) or regulatory cytokines, interleukin-10 (IL-10), and IL-13)[2,3]
An ongoing trial of a dendritic cell (DC) vaccine transduced with an adenovirus expressing the extracellular and transmembrane domains of HER2, which cures mice of HER2+ tumors by inducing antibodies, is resulting in some complete and partial responses and stable disease in close to 50% of vaccinated patients with advanced metastatic HER2-expressing cancers who have failed standard therapies (Maeng et al, manuscript in preparation)
Summary
Cancer vaccines have been extensively researched in both animal models and humans over the past 30 years across many different types of cancer. A whole allogeneic pancreatic cell line secreting GM-CSF, called GVAX, is another strategy to use DCs in vivo that stimulate the accrual and function of APCs to the vaccine site This strategy can potentially involve all DC subsets, the subsets in the apheresis product, and result in increased T-cell infiltration and development of tertiary lymphoid structures even in a so-called “non-immunogenic” tumor such as pancreatic cancer or prostate cancer[143,144]. The majority of the vaccines that were successful in inducing immunologic anti-tumor response could not match that success in the clinical response, indicating the need for improved vaccine platforms and probably combinations with checkpoint inhibitors or other methods to block immune suppression by cancer
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