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

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 o...

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Published in:The oncologist (Dayton, Ohio) Ohio), 2023-06, Vol.28 (6), p.e406-e415
Main Authors: Yarza, Ramon, Bover, Mateo, Herrera-Juarez, Mercedes, Rey-Cardenas, Macarena, Paz-Ares, Luis, Lopez-Martin, Jose A, Haanen, John
Format: Article
Language:English
Subjects:
Antigen receptors, T cell
Cancer
Care and treatment
Cellular therapy
Health aspects
Humans
Immunotherapy, Adoptive
Male
Melanoma
Melanoma - pathology
Melanoma and Cutaneous Malignancies
Melanoma, Cutaneous Malignant
Oncology, Experimental
Receptors
Receptors, Antigen, T-Cell - genetics
Skin cancer
Skin Neoplasms - therapy
T cells
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Summary: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 of TCR-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 for TILs 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). Adoptive Cell Therapy represents a novel therapeutic modality in cancer. To this extent, TCR based ACT modelling has become a suitable strategy with the aim of targeting specific tumour associated antigens. This works provides a pool metanalysis of the efficacy and antitumor activity of TCR based ACT experience in metastatic cutaneous melanoma.
ISSN:1083-7159
1549-490X
DOI:10.1093/oncolo/oyad078