Purpose: Neoantigens produced from mutations in tumors are important targets of T-cell-based immunotherapy and immune checkpoint blockade has been approved for treating multiple solid tumors. We investigated the potential benefit of adoptive neoantigen-reactive T (NRT) cells in combination with programmed cell death protein 1 inhibitor (anti-PD1) for treating lung cancer in a mouse model.
Methods: NRT cells were prepared by co-culturing T cells and neoantigen-RNA vaccine-induced dendritic cells. Then, adoptive NRT cells in combination with anti-PD1 were administered to tumor-bearing mice. Pre- and post-therapy cytokine secretion, antitumor efficacy, and tumor microenvironment (TME) changes were determined both in vitro and in vivo.
Results: We successfully generated NRT cells based on the 5 neoantigen epitopes identified in this study. NRT cells exhibited an enhanced cytotoxic phenotype in vitro and the combination therapy led to attenuated tumor growth. In addition, this combination strategy downregulated the expression of the inhibitory marker PD-1 on tumor-infiltrating T cells and promoted the trafficking of tumor-specific T cells to the tumor sites.
Conclusion: The adoptive transfer of NRT cells in association with anti-PD1 therapy can exert an antitumor effect on lung cancer, and is a feasible, effective, and novel immunotherapy regimen for treating solid tumors.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10024025 | PMC |
| http://dx.doi.org/10.1007/s00432-023-04683-5 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Delivery of IL-12 by neoantigen-reactive T cells promotes antitumor immunity in murine osteosarcoma mode.
Immunother Adv
November 2024
Department of Oncology, Shanghai Jiao Tong UniversityAffiliated Sixth People' s Hospital, Shanghai 201306, China.
Purpose: Despite the proven clinical benefits of cytokine therapy in cancer treatment, systemic administration of cytokines such as IL-12 is constrained by dose-limiting toxicities and short half-lives. To address these challenges, we explored a localized cytokine delivery strategy using engineered neoantigen-reactive T (NRT) cells as carriers in a murine model of osteosarcoma.
Materials And Methods: We used a neoantigen from K7M2 osteosarcoma cells to retrovirally transduce NRT cells to express an inducible form of IL-12.
Heterogeneity in response to neoadjuvant radiotherapy between soft tissue sarcoma histotypes: associations between radiology and pathology findings.
Eur Radiol
December 2024
Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Objective: To investigate imaging biomarkers of tumour response by describing changes in imaging and pathology findings after neoadjuvant radiotherapy (nRT) and exploring their correlations.
Materials And Methods: Tumour diameter, volume, and tumour-to-muscle signal intensity (SI) ratio were collected before and after radiotherapy in a cohort of 107 patients with intermediate/high-grade STS and were correlated with post-radiotherapy pathology findings (percentage of necrosis, viable cells, and fibrosis) using Spearman Rank test. Pathological complete response (pCR) was defined as no residual viable cells present, whereas the presence of < 10% viable cells was defined as near-complete pathologic response (near-pCR).
Exploring the tumor microenvironment of colorectal cancer patients post renal transplantation by single-cell analysis.
Cancer Sci
December 2024
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Article Synopsis
- * Analysis through single-cell RNA sequencing identified significant changes in immune cell function in transplant recipients, including reduced cytotoxicity in CD8 T cells and increased inhibitory activity in regulatory T cells within tumors.
- * Findings highlight the potential for developing targeted immunotherapies to improve patient outcomes in renal transplant recipients with colorectal cancer, based on the unique immune landscape observed.
A dendritic cell vaccine for both vaccination and neoantigen-reactive T cell preparation for cancer immunotherapy in mice.
Nat Commun
November 2024
Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Article Synopsis
- Adoptive cell transfer (ACT) using T cells that target neoantigens shows promise in cancer treatment, but isolating these specific T cells is challenging.
- A new method has been proposed to prepare neoantigen-reactive T cells (NRTs) using a vaccine made from tumor lysates and dendritic cells, which generates an immune response in lung cancer models.
- This approach allows for effective NRT preparation and enhances their ability to infiltrate tumors when combined with DC vaccines, potentially improving the overall efficacy of personalized immunotherapies.
Depletion of regulatory T cells enhances the T cell response induced by the neoantigen vaccine with weak immunogenicity.
Neoplasia
January 2025
Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Second Military Medical University, Shanghai, 200433, PR China; Center of Critical Care Medicine, the First Affiliated Hospital of Second Military Medical University, Shanghai, 200433, PR China. Electronic address:
Background: The neoantigen vaccine has remarkable potential in treating advanced cancer due to its tumor specificity and ability to bypass central tolerance mechanisms. However, numerous neoantigens show poor immunogenicity, and the immune inhibitory factors of present in both tumors and tumor-draining lymph nodes impair the efficacy of cancer neoantigen vaccine. Eliminating immunosuppressive cells will improve the priming and expansion of anti-tumor immune cells induced by the vaccine.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!