Related Experiment Video
Updated: Jun 27, 2025
Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Long-Term Survival and Immune Response Dynamics in Melanoma Patients Undergoing TAPCells-Based Vaccination Therapy
Andrés Tittarelli1, Cristian Pereda2, María A Gleisner2,3
1Programa Institucional de Fomento a la Investigación, Desarrollo e Innovación, Universidad Tecnológica Metropolitana, Santiago 8940577, Chile.
Abstract:
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, DTHpos patients exhibit a 53.1% three-year survival compared to 16.1% in DTHneg patients. Extended remissions are observed in long-term survivors, particularly DTHpos/M1cneg 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 M1cneg/DTHpos 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.
Insights
Tumor antigen-presenting cell vaccines (TAPCells) show promise for melanoma patients refractory to immune checkpoint blockers. Delayed-type hypersensitivity (DTH) positivity correlates with significantly improved long-term survival and remission.
Area of Science:
- Oncology
- Immunology
- Vaccine Therapy
Background:
- Cancer vaccines offer a potential treatment strategy for patients with immune checkpoint blocker (ICB)-refractory melanoma.
- Tumor antigen-presenting cells (TAPCells) are autologous vaccines loaded with heat-shocked allogeneic melanoma cell lysates.
Purpose of the Study:
- To extend the analysis of a phase I/II trial (NCT06152367) of TAPCells, investigating long-term outcomes and novel associations with clinical, genetic, and immunologic parameters.
- To identify predictive markers for long-term remission in melanoma patients treated with TAPCells.
Main Methods:
- A 15-year follow-up analysis of patients treated with TAPCells.
- Categorization of patients into short-term (<36 months) and long-term (≥36 months) survivors.
- Exploration of associations between clinical outcomes and demographic, genetic (e.g., TLR-4 polymorphism), and immunologic markers (e.g., DTH reactions, specific cell populations, cytokines).
Main Results:
- Delayed-type hypersensitivity (DTH) positivity was strongly associated with improved three-year survival (53.1% vs. 16.1% for DTH-negative).
- Long-term survivors, particularly DTH-positive/M1c-negative patients, exhibited extended remissions.
- Specific immunomarkers (increased C-type lectin domain family 2 member D on CD4+ T cells, elevated IL-17A) were linked to better outcomes, while others (TLR-4 D229G, reduced CD32 on B cells) correlated with poorer survival.
- TAPCells induced stable long remissions in 35.2% of patients, especially in the DTH-positive/M1c-negative subgroup.
Conclusions:
- Vaccine-induced immune responses, particularly DTH, are crucial for achieving long-term remission in melanoma.
- Identification of novel predictive biomarkers (immunologic and genetic) can guide treatment strategies and patient selection for TAPCell therapy.
- TAPCells demonstrate potential for inducing durable responses in a subset of ICB-refractory melanoma patients.
