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A treatment that finds the rare T cells in a patient's own blood that already recognise the cancer, grows large numbers of them in the laboratory without changing their genes, and infuses them back.
Yee, Lizee and Schueneman describe three ways of adoptive T-cell transfer: tumour-infiltrating lymphocytes taken from a biopsy; lymphocytes redirected by a chimeric antigen receptor or T-cell receptor; and the isolation and expansion of often low-frequency endogenous T cells reactive to tumour antigens from the peripheral blood, which they call endogenous T-cell (ETC) therapy (Cancer Journal 2015). It needs specialised methods to isolate and expand very low-frequency tumour-reactive T cells from blood, and the authors note that a trial can be started quickly once a tumour-associated target epitope has been identified (Cancer Journal 2015). The early melanoma trials at Fred Hutchinson Cancer Research Center infused such cells as clones against MART-1, gp100, tyrosinase and NY-ESO-1.
Showing the technology this term belongs to: TIL therapy.
Combining antigen-specific T cells with CTLA-4 blockade was safe in this small study and produced durable responses, supporting checkpoint inhibitors as partners for cell therapy.
The paper gives the approach its name and makes the case for it beyond melanoma.
An overview of the endogenous T-cell approach from one of its developers, written as checkpoint inhibitors and engineered cell therapies were entering the clinic.
Infused T-cell clones can convert to a central memory type in the body, which may underlie lasting benefit.
Lymphodepletion before infusion helps transferred T cells survive, but the rise in regulatory T cells suggests conditioning alone is not enough for anti-tumour effect.
Helper (CD4+) T cells, not only killer (CD8+) T cells, can drive a remission, and one targeted infusion can widen the immune response to other tumour antigens.
It showed that T cells taken from a patient's blood, selected for one melanoma antigen and grown as clones, can survive after infusion, reach tumours and kill the antigen-carrying cells there.
Targeting a protein that tumours share with normal cells can damage those normal cells too; the authors state this was the first direct evidence of it in humans, which shaped later thinking on on-target, off-tumour toxicity.
Shares Melanocyte destruction after antigen-specific immunotherapy of melanoma: direct evidence of T cell-mediated vitiligo, Autologous CD4+ antigen-specific T-cell clones in advanced ovarian or primary peritoneal cancer (Fred Hutchinson phase 1), Autologous CD4+ antigen-specific T-cell clones in metastatic melanoma (Fred Hutchinson phase 1), T-Cell Therapy Using Interleukin-21-Primed Cytotoxic T-Cell Lymphocytes Combined With Cytotoxic T-Cell Lymphocyte Antigen-4 Blockade Results in Long-Term Cell Persistence and Durable Tumor Regression.
Shares CD8+ antigen-specific T-cell clones after cyclophosphamide, with aldesleukin, in stage IV melanoma (Fred Hutchinson phase 1/2, NCI-2010-01281), CD8+ T-cell clones against cancer-testis antigens in metastatic melanoma (Fred Hutchinson phase 1), Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells, Transferred melanoma-specific CD8+ T cells persist, mediate tumor regression, and acquire central memory phenotype.
Shares Treatment of metastatic melanoma with autologous CD4+ T cells against NY-ESO-1, Autologous CD4+ NY-ESO-1-specific T cells with ipilimumab in NY-ESO-1-expressing tumours (MD Anderson phase 1, withdrawn), Cassian Yee.
Shares Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells, Cassian Yee, TCR-T cell therapy, Melanoma.
Shares Fludarabine modulates immune response and extends in vivo survival of adoptively transferred CD8 T cells in patients with metastatic melanoma, Fludarabine before CD8+ antigen-specific T-cell clones in stage IV melanoma (Fred Hutchinson phase 1), CAR-T cell therapy.
Shares TCR-T cell therapy, TIL therapy, CAR-T cell therapy.
Shares Tyrosinase-specific CD8+ T cells, gene-modified and unmodified, in metastatic melanoma (Fred Hutchinson phase 1/2), Melanoma.
Shares TCR-T cell therapy, TIL therapy, Melanoma.
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