Vaccinating against cancer: getting to prime time

Abstract

Immunotherapies, such as immune checkpoint inhibitors, cellular therapies, and T-cell engagers, have fundamentally changed our approach to treating cancer. However, successes with cancer vaccines have been more difficult to realize. While vaccines against specific viruses have been widely adopted to prevent the development of cancer, only two vaccines can improve survival in advanced disease: sipuleucel-T and talimogene laherparepvec. These represent the two approaches that have the most traction: vaccinating against cognate antigen and priming responses using tumors in situ. Here, we review the challenges and opportunities researchers face in developing therapeutic vaccines for cancer.

Targeted immunotherapy for glioblastoma involving whole tumor-derived autologous cells in the upfront setting after craniotomy

“…Unlike most other immunotherapies, cancer vaccines typically have minimal side effects, as they rely on the selection of highly immunogenic tumor antigens that are only expressed by cancer cells. Tumor antigens can be classified as tumor-associated antigens (TAAs) or tumor-specific antigens (TSAs) [ 10 , 17 ]. TAAs are preferentially overexpressed on tumor cells but can be present in healthy cells, or they may be cancer/testis antigens that are only expressed by tumor cells and adult reproductive tissues.…”

“…TAAs are preferentially overexpressed on tumor cells but can be present in healthy cells, or they may be cancer/testis antigens that are only expressed by tumor cells and adult reproductive tissues. TSAs, conversely, are de novo epitopes expressed by oncoviruses and shared or individual-specific neoantigens encoded by somatic mutations [ 17 ]. Compared to cancer vaccines that use TAAs or TSAs to induce tumor-reactive T cells, whole tumor-derived approaches have the benefit of being truly antigen-inclusive.…”

Induction of long-term tolerance to a specific antigen using anti-CD3 lipid nanoparticles following gene therapy

“… 21 , 37 , 38 , 39 , 40 , 41 , 42 , 43 To date, therapeutic mAbs encoded by mRNA LNPs have been used and reported in numerous preclinical and clinical studies. 16 , 18 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 An mRNA LNP-based therapeutic mAb expression system has several potential advantages over recombinant mAbs for the treatment of patients. The variation of recombinant products produced in different cell systems can be diminished.…”

Extracellular vesicles as human therapeutics: A scoping review of the literature

“…The oldest studies selected in the present review present data on the clinical testing the EVs in the field of cancer immunotherapy; this approach, generally aimed at strengthening or inducing host antitumor immune response, is now an established therapeutic option adding to the traditional chemo‐ and radiotherapy to treat both haematological and solid malignancies (Esfahani et al., 2020 ). In particular, the adoptive transfer of autologous dendritic cells (DC) pulsed with tumour peptides to drive anti‐tumour specific T cell responses, approved by the Food and Drug Administration (FDA) in 2010, was demonstrated to prolong survival of metastatic castration‐resistant prostate cancer patients (Chang et al., 2023 ; Kantoff et al., 2010 ) The possible development of an alternative vaccination strategy, based on tumour antigen‐presenting EVs of DC origin, was suggested by a milestone paper published at the end of last century which demonstrated that the EVs released by cancer peptide‐pulsed DCs could prime cytotoxic T cells and induce the rejection of established tumours in mice (Zitvogel et al., 1998 ). EVs were hypothesized to have the advantage of expressing high levels of antigens, in combination with costimulatory molecules; as a matter of fact, DC‐derived EVs were characterized at the molecular level and the procedures for their purification and storage optimized (Lamparski et al., 2002 ; Théry et al., 2001 ).…”