Adoptive cell therapy with CD4+ T helper 1 cells and CD8+ cytotoxic T cells enhances complete rejection of an established tumour, leading to generation of endogenous memory responses to non‐targeted tumour epitopes. Issue 10 (20th October 2017)

• Record Type: Journal Article
• Authors: Li, Kunyu; Donaldson, Braeden; Young, Vivienne; Ward, Vernon; Jackson, Christopher; Baird, Margaret; Young, Sarah
• Is Part Of: Clinical & translational immunology. Volume 6:Issue 10 (2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-10-20
• Subjects: Immunologic diseases -- Periodicals; Immunology -- Periodicals; Clinical medicine -- Periodicals; Immune System Diseases -- therapy; Immunotherapy; Immunologic Factors -- therapeutic use; Translational Medical Research; Molecular Targeted Therapy; Clinical medicine; Immunologic diseases; Immunology; Periodicals; Periodicals; Fulltext; Internet Resources; Periodicals; 616.079
• DOI: 10.1038/cti.2017.37
• Languages: English
• ISSNs: 2050-0068

Abstract

Abstract : The results of adoptive T‐cell therapies (ACTs) are very encouraging and show clinical evidence that ACT can provide a cure for patients with metastatic disease. However, various response rates and long‐term cancer remission have been observed in different ACT trials. The types of T cells, prior treatment with chemotherapy and co‐administration of other immune‐target therapies have been found to influence the efficacy of ACT. In this study, we investigate the ability of ACT using CD4 + T helper 1 (Th1) cells and CD8 + cytotoxic T lymphocytes (CTLs) to reject the growth of established B16‐ovalbumin (OVA) melanoma. CD8 + CTLs were found to be the main effector T cells that mediated tumour regression. However, low tumour‐free survival rates were observed in ACT with CD8 + CTLs only. Co‐transferring CD4 + Th1 cells and CD8 + CTLs has been observed to induce a synergistic antitumour response, resulting in complete regression in 80% of the tumour‐bearing mice. We also examined a prior Dacarbazine (DTIC) and after virus‐like particle (VLP)‐OVA vaccine treatment to enhance ACT, but no therapeutic benefit was observed during primary B16‐OVA tumour growth. Nevertheless, the ACT‐mediated antitumour response was able to generate memory responses to both B16‐OVA and B16‐gp33 tumours. VLP‐OVA vaccination following ACT enhances the memory responses to tumours that express a heterogenic population of both B16‐OVA and B16‐gp33 cells; however, it abolished the memory response to tumours consisting of only gp33‐expressing cells. These findings provide important information for designing therapeutic treatments for patients with metastatic disease and cancer relapse to achieve durable cancer remission. Cancer: Combination T cell therapy shows potent anti‐tumor activity: Transferring a combination of "helper" T cells and "cytotoxic" T cells into mice results in a synergistic anti‐cancer response. Adoptive T cell therapy is a highly personalized cancer treatment in which tumor‐reactive T cells are isolated from a patient, grown in the laboratory, and then reinfused into the same patient. There are many variations on this strategy, and Sarah Young and colleagues from the University of Otago in Dunedin, New Zealand, investigated a combination approach in mouse models of melanoma. They showed that adding helper T‐cells, which are known to assist in activating cytotoxic T‐cells, shrank tumors more than treatment with cytotoxic T‐cells alone. Adding an anti‐cancer vaccine after the adoptive T‐cell transfer enhanced immune memory responses, which could help prevent metastasis or cancer relapse. These findings could help in designing similar treatments for cancer patients.