Adenoviral vaccines promote protective tissue-resident memory T cell populations against cancer

Abstract

BackgroundAdenoviral vectors emerged as important platforms for cancer immunotherapy. Vaccination with adenoviral vectors is promising in this respect, however, their specific mechanisms of action are not fully understood. Here, we assessed the development and maintenance of vaccine-induced tumor-specific CD8+ T cells elicited upon immunization with adenoviral vectors.MethodsAdenoviral vaccine vectors encoding the full-length E7 protein from human papilloma virus (HPV) or the immunodominant epitope from E7 were generated, and mice were immunized intravenously with different quantities (107, 108 or 109 infectious units). The magnitude, kinetics and tumor protection capacity of the induced vaccine-specific T cell responses were evaluated.ResultsThe adenoviral vaccines elicited inflationary E7-specific memory CD8+ T cell responses in a dose-dependent manner. The magnitude of these vaccine-specific CD8+ T cells in the circulation related to the development of E7-specific CD8+ tissue-resident memory T (TRM) cells, which were maintained for months in multiple tissues after vaccination. The vaccine-specific CD8+ T cell responses conferred long-term protection against HPV-induced carcinomas in the skin and liver, and this protection required the induction and accumulation of CD8+ TRM cells. Moreover, the formation of CD8+ TRM cells could be enhanced by temporal targeting CD80/CD86 costimulatory interactions via CTLA-4 blockade early after immunization.ConclusionsTogether, these data show that adenoviral vector-induced CD8+ T cell inflation promotes protective TRM cell populations, and this can be enhanced by targeting CTLA-4.

A Novel Immunomodulator Delivery Platform Based on Bacterial Biomimetic Vesicles for Enhanced Antitumor Immunity

“…On the other hand, because the E7 sequence suitable for human use has not been determined, the application of full-length E7 will have more clinical development value. [49] Although CD4 + Th1 cells and CD8 + CTLs are the main antitumor cell groups, the use of the full-length E7 protein here may also induce CD4 + Th2 responses. Based on previous studies on OMVs, this bacterial-membrane-based delivery system has been proven to bias the immune balance more towards the Th1 response; [50] thus, this bacterial membrane carrier can better promote CD8 + T cell responses.…”

A third vaccination with a single T cell epitope protects against SARS-CoV-2 infection in the absence of neutralizing antibodies

“…Single B and T cell epitope vaccines can provide effective approaches against a variety of pathogens and malignancies (21–24). To investigate the efficacy of linear B cell epitope vaccines against SARS-CoV-2 infection, we selected five different linear epitopes present in the Spike protein that were considered to potentially elicit protective antibodies (25–27).…”

The Emerging Role of Tissue-Resident Memory CD8+ T Lymphocytes in Human Digestive Tract Cancers

“…In addition, encoding respiratory syncytial virus mechanisms or recombinant cytomegalovirus vectors of Bacille Calmette-Guerin vaccine proteins for intranasal vaccination promotes immune cells to develop resident properties (101,102). The vaccine-specific CD8 + T cell response can provide long-term protection against HPV-induced skin cancer and HCC but is dependent on the induction and accumulation of CD8 + Trm cells by blocking CTLA-4 early after immunization (61). Local radiotherapy by vaccination (103), which changes the expression of selectin, integrin, and chemokines, can also enhance the recruitment of resident CD8 + T lymphocytes in the tissue and tumor site.…”