Long-Term Survival and Immune Response Dynamics in Melanoma Patients Undergoing TAPCells-Based Vaccination Therapy

• Published in: Vaccines (Basel) Vol. 12; no. 4; p. 357
• Main Authors: Tittarelli, Andrés, Pereda, Cristian, Gleisner, María A, López, Mercedes N, Flores, Iván, Tempio, Fabián, Lladser, Alvaro, Achour, Adnane, González, Fermín E, Durán-Aniotz, Claudia, Miranda, Juan P, Larrondo, Milton, Salazar-Onfray, Flavio
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.04.2024
• Subjects: Analysis; Antigen-presenting cells; Antigens; B cells; BCG; BCG vaccines; Biomarkers; Blood; Cancer therapies; Cancer vaccines; Care and treatment; CD4 antigen; Cells; Clinical outcomes; Clinical trials; compassionate use; dendritic cell; Hypersensitivity; Hypersensitivity (delayed); Immune checkpoint; Immune response; Immune system; Immunology; Immunotherapy; Interferon; Leukocytes; Lymphatic system; Lymphocytes; Lymphocytes B; Lymphocytes T; Lysates; Medical research; Medicin och hälsovetenskap; Medicine, Experimental; Melanoma; Metastasis; Parameter identification; Patient outcomes; Patients; Polymorphism; Remission; Skin cancer; Survival; T cells; Toll-like receptors; Tumor microenvironment; Tumors; Vaccination; vaccine; Vaccines; Chile; California; United States > US; vaccine; immunotherapy; overall survival; DTH; melanoma; clinical trials; compassionate use; dendritic cell
• ISSN: 2076-393X; 2076-393X
• DOI: 10.3390/vaccines12040357

Cancer vaccines present a promising avenue for treating immune checkpoint blockers (ICBs)-refractory patients, fostering immune responses to modulate the tumor microenvironment. We revisit a phase I/II trial using Tumor Antigen-Presenting Cells (TAPCells) (NCT06152367), an autologous antigen-presenting cell vaccine loaded with heat-shocked allogeneic melanoma cell lysates. Initial findings showcased TAPCells inducing lysate-specific delayed-type hypersensitivity (DTH) reactions, correlating with prolonged survival. Here, we extend our analysis over 15 years, categorizing patients into short-term (<36 months) and long-term (≥36 months) survivors, exploring novel associations between clinical outcomes and demographic, genetic, and immunologic parameters. Notably, DTH patients exhibit a 53.1% three-year survival compared to 16.1% in DTH patients. Extended remissions are observed in long-term survivors, particularly DTH /M1c patients. Younger age, stage III disease, and moderate immune events also benefit short-term survivors. Immunomarkers like increased C-type lectin domain family 2 member D on CD4 T cells and elevated interleukin-17A were detected in long-term survivors. In contrast, toll-like receptor-4 D229G polymorphism and reduced CD32 on B cells are associated with reduced survival. TAPCells achieved stable long remissions in 35.2% of patients, especially M1c /DTH cases. Conclusions: Our study underscores the potential of vaccine-induced immune responses in melanoma, emphasizing the identification of emerging biological markers and clinical parameters for predicting long-term remission.