Peptide therapy bypasses the need for vaccination and taps into adaptive cytotoxic memory T-cell populations that have already passed through these regulatory checkpoints in order to control pathogens. Oncolytic virotherapies have shown exciting promise and while originally used as a targeted way to kill tumor cells, this therapy also induces anti-tumor immunostimulatory effects. Because of the nature of the therapy a live replicating virus , induction of an antiviral immune response can work to inhibit the therapy.
Additionally, there are viruses currently being tested, such as herpesviruses, poliovirus and measles virus, that may stimulate pre-existing immunity. Presence of antibodies specific to the virotherapy can pose a challenge as this can inhibit infection and potentially limit efficacy Despite these limitations, clinical trials have demonstrated promising efficacy, in particular with T-VEC, an oncolytic herpesvirus that has demonstrated efficacy against melanoma when injected intratumorally 26 , While not tested, an intriguing possibility is that some current virotherapies may be tapping into pre-existing T-cell immunity specific to those viruses which may exist in tumors.
Immunotherapies that more directly work to induce an anti-tumor T-cell response have also shown exciting promise and include vaccines targeting tumor antigens, checkpoint blockade, and adoptive cell therapies including chimeric antigen receptor CAR T-cell therapy, however, clinical efficacy against solid tumors remains suboptimal or does not work for many patients 4.
A potential disadvantage is that viral peptides may have to be matched to patient HLA type. HLAs, however, are easy to assess, are shared by large populations, and peptides from ubiquitous human pathogens have already been defined for common HLAs. Additionally, these issues may be counterbalanced by safety and manufacturing advantages as relevant synthetic viral peptides are only 8—10 amino acids. Moreover, peptide therapy requires no adjuvant, vaccine, or replicating agent potentially subject to risky safety profiles or issues with dosing and tropism, nor costly identification of tumor-specific antigens that may not be immunogenic.
In summary, re-stimulating known antiviral immunity via defined peptides from common pathogens provides a unique therapeutic avenue for cancer immunotherapy. Sample size was chosen on the basis of previous experience. No sample exclusion criteria were applied.
No method of randomization was used during group allocation, and investigators were not blinded. All mice used in experiments were 5—14 weeks of age. We used an intravascular staining method to discriminate cells present in the vasculature from cells in the tissue parenchyma, as described 28 for h timepoints.
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In brief, we injected mice i. Three minutes after the injection, we euthanized the animals and harvested tissues as described Cell viability was determined with Ghost Dye Tonbo Biosciences.
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Enumeration of cells was done using PKH26 reference microbeads Sigma. The sucrose-treated tissue was embedded in OCT tissue-freezing medium and frozen in an isopentane liquid bath. For local tumor T cell reactivation experiments involving peptides, 0. All tumor tissue and blood was obtained from male or female patients age 16—80 undergoing routine surgical resection of solid tumors or tumor metastases. Tumor tissue not required for pathological diagnostic procedures was obtained after surgical resection at the University of Minnesota and collected and de-identified by the Tissue Procurement Facility BioNet, University of Minnesota.
Informed consent was obtained from all subjects. Human blood was processed by Ficoll gradient.
Cells were stained at antibody dilutions of Tumors were sliced into thin sections manually with a sharp surgical blade. Tissues with poor viability after culture were excluded.
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