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Immunomodulatory Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Cell-based therapies such as dendritic cell-based cancer vaccines are another platform for novel cancer vaccines. These involve extraction of dendritic cells (DCs) from the patient’s blood which are then cultured with a source of TAAs before administering back into the patient’s circulation. Whole tumor cells can be used in these vaccines, and the advantage of this is that a variety of tumor-associated antigens can be presented to the immune system, thereby eliciting immune responses to multiple antigens and potentially inducing a longer-lasting immune response. However, a relative lack of specificity in relation to multiple antigens can sometimes dilute the immune response. Therefore, additional stimulation of the immune system with an adjuvant such as Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) can be helpful for this platform. Cell-based cancer vaccines can be further divided into autologous and allogeneic treatments. The former involves the use of the patient’s own tumor cells to develop the vaccine, which is then referred to as an autologous tumor cell vaccine. The use of tumor cells from one patient for use in a second patient produces an allogeneic tumor cell vaccine. Autologous tumor cell vaccines were among the first type of cancer vaccines to be developed and evaluated. The early versions involved mixing Bacillus Calmette-Guérin (BCG) with tumor cells and using this mixture to treat mice with visceral micro-metastases which proved successful. There is a view that allogeneic vaccines are more likely to become commercially successful as they can be produced and then supplied “off the shelf” to multiple patients, making this a faster and cheaper option compared to the time and expense associated with producing autologous vaccines for individual patients.
T cell recognition of novel shared breast cancer antigens is frequently observed in peripheral blood of breast cancer patients
Published in OncoImmunology, 2019
Nadia Viborg, Sofie Ramskov, Rikke Sick Andersen, Theo Sturm, Tim Fugmann, Amalie Kai Bentzen, Vibeke Mindahl Rafa, Per thor Straten, Inge Marie Svane, Özcan Met, Sine Reker Hadrup
Several of the ex vivo observed CD8+ T cell responses were verified after in vitro expansion, with expanded responses from two patient samples validated by fluorescently-labeled pMHC multimer staining. In addition to observing CD8+ T cell responses ex vivo, and after specific expansion, a subset of breast cancer patient samples were further investigated for functional capacity upon stimulation and ICS. Interestingly, the functional analysis revealed breast cancer patient CD8+ T cell reactivity to some of the TAA-derived peptides that were observed in ex vivo screenings. A limitation of the study is the lack of patient autologous tumor cells. Although we document T cell recognition of allogeneic, commercially available cancer cell lines, the pairing of patient T cells and autologous tumor cell lines would enable verification of autologous recognition. The same limitation applies to the mass spectrometry analysis, where MHC class I expression of peptides from all four proteins was investigated in three commercially-available breast cancer cell lines. Here one putative HLA-A*02:01 ligand (PIAS3; SIVAPGGAL) identified by mass spectrometry was overlapping with the T cell screening peptide library. This peptide did not result in T cell responses. Despite the limited overlap, the detection of four MHC class I embedded PIAS3 peptides does document expression and antigen-processing of PIAS3 in breast cancer.