Efficacy of T-Cell Receptor-Based Adoptive Cell Therapy in Cutaneous Melanoma - A Meta-Analysis

Sep 28, 2026

Uploaded by Rhys

T-cell receptor (TCR-T) therapies introduce TCRs targeting tumor-associated antigens (TAA), with evidence from multiple cutaneous melanoma trials. A systematic review and meta-analysis evaluated the primary efficacy of TCR-based adoptive cell therapy in cutaneous melanoma using pooled objective response rate (ORR) and disease control rate (DCR), plus logistic regression for predictive factors. Results included pooled ORR of 28% and DCR of 38%, with dose- and antigen-targeting-associated differences in progression-free survival.

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CategoryHealthcare

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Efficacy ofT-Cell Receptor-Based Adoptive Cell Therapy in Cutaneous Melanoma: A Meta-Analysis Ramon Yarza*, 1,, Mateo Bover1, Mercedes Herrera-Juarez1, Macarena Rey-Cardenas1, Luis Paz-Ares1, Jose A. Lopez-Martin2,3, John Haanen4 1Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain 2Virology and Inflammation Unit, PharmaMar, SA, Madrid, Spain 3GETICA (Spanish Group for Cancer Immuno-Biotherapies), Madrid, Spain 4Division of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands *Corresponding author: Ramon Yarza, Department of Medical Oncology, Hospital Universitario 12 de Octubre, Avda Cordoba s/n, E-280241 Madrid, Spain. Tel:+34 914 603 310. Email [ramon.yarza@salud.madrid.org](ramon.yarza@salud.madrid.org) Abstract Background: T-cell receptor (TCR-T) therapies are based on the expression of an introduced TCR targeting a tumor associated antigen (TAA) which has been studied in several trials in cutaneous melanoma. We conducted a systematic review and meta-analysis aiming to assess the primary efficacy ofTCR-based adoptive cell therapy in cutaneous melanoma. Methods: We searched through PubMed electronic database from its inception until May 21, 2022. Primary endpoints were pooled objective response rate (ORR) and disease control rate (DCR) . We conducted logistic regression analyses to identify potential predictive factors for tumor response. Results: From 187 patients, 50 showed an objective response (pooled ORR 28%; 95% CI, 20%-37%) and a pooled DCR of 38%(95% CI, 27%-50%) . Median PFS was 2, 9 months (95% CI, 1.4-3. 1) . A trend toward higher PFS was demonstrated for patients treated with cancer/testis antigens targeting TCR-T cells (HR 0.91 95% CI, 0.64-1.3, P = .61) among whom, patients treated with NYESO-1 targeting TCR-T showed a significantly higher PFS (HR 0.63 95% CI, 0.64-0.98, P = .03) . In addition, the number of infused cells was associated with a significantly higher likelihood of tumor response (OR 6.61; 95% CI, 1.68-21.6; P = .007) . Conclusion: TCR-T therapy shows promising results in terms of antitumor activity and survival similar to those reported forTILs with a significantly higher benefit for cancer/testis antigens targeting cells. Since TCR-based therapy shows advantages of great potential over classic ACT strategies, further research in solid cancers is warranted (PROSPERO ID CRD42022328011) . Key words: adoptive cell therapy; T-cell receptor; cutaneous melanoma; meta-analysis. Abbreviations: ACT, adoptive cell therapy; CAR, chimeric antigen receptor; CAR-T, chimeric antigen receptor T cell; CR, complete response; DC, dendritic cell; DCR, disease control rate; DoR, duration of response; DoS, duration of stability; FEM, fixed effect model; gp100, glycoprotein 100; HD, high-dose; HLA, human leukocyte antigen; HR, hazard ratio; ICB, immune checkpoint blockade; iCTLA-4, cytotoxic T-lymphocyte associated protein 4 inhibitor; IL2, interleukin 2; iPD1, programmed death 1 inhibitor; LD, low-dose; MAGE-A3, melanoma-associated antigen 3; MART1, melan-A; melanoma antigen recognized by T cells; MHC, major histocompatibility complex; NMA, non-myeloablative; NYESO-1, New York esophageal squamous cell carcinoma 1; OR, odds ratio; ORR, objective response rate; OS, overall survival; PD, progression disease; PFS, progression-free survival; PR, partial response; REM, random effect model; scFv, single chain variable fraction; SD, stable disease; SMAC, supramolecular activation cluster; TAA, tumor associated antigen; TCR, T-cell receptor; TCR-T, T-cell receptor T cell; TIL, tumor-infiltrating lymphocyte Implications for Practice Adoptive cell therapy aims to target cancer cells by genetically engineered immune cells with the objective of enhancing tumor recognition and effective tumor killing. We demonstrate that TCR-T-based ACT has similar efficacy results compared to those reported forTILs among heavily pretreated melanoma patients. We also

FAQs

What was the main objective of the systematic review and meta-analysis?

To assess the primary efficacy of TCR-based adoptive cell therapy in cutaneous melanoma, using pooled objective response rate (ORR) and disease control rate (DCR).

How effective was TCR-T therapy according to pooled results?

Among 187 patients, 50 showed an objective response with a pooled ORR of 28%, and the pooled DCR was 38%. Median progression-free survival was 2.9 months.

Which factors were associated with better tumor response or longer PFS?

Higher likelihood of tumor response was associated with the number of infused cells. Patients treated with TCR-T cells targeting cancer/testis antigens showed a trend toward higher PFS, and NYESO-1 targeting TCR-T was linked to significantly higher PFS.

Sep 28, 2026

Uploaded by Rhys