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Updated: May 11, 2026
Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors
Published on: December 16, 2022
Comparative analysis of cancer vaccine settings for the selection of an effective protocol in mice
Francesca Kalli1, Rodolfo Machiorlatti, Florinda Battaglia
1Centre of Excellence for Biomedical Research, University of Genoa, Viale Benedetto XV n. 7, 16132, Genoa, Italy.
Background:
Cancer vaccines are considered a promising therapeutic approach. However, their clinical results are not yet satisfactory. This may be due to the the difficulty of selection of an efficient tumor associated antigen (TAA) and immunization protocol. Indeed, the weak antigenicity of many TAA impairs the design of robust procedures, therefore a systematic analysis to identify the most efficient TAA is mandatory. Here, we performed a study to compare different gp100 vaccination strategies to identify the best strategy to provide a 100% protection against experimental melanoma in a reproducible manner.
Methods:
C57BL/6J mice were challenged subcutaneously with B16F10 melanoma cells, after vaccination with: a) mouse or human gp10025-33 peptide plus CpG adjuvant; b) mouse or human gp100 gene; c) mouse or human gp10025-33 peptide-pulsed dendritic cells (DC). Alternatively, a neutralizing anti-IL-10 monoclonal antibody (mAb) was subcutaneously administered at the site of tumor challenge to counteract regulatory cells. Finally, combinatorial treatment was performed associating human gp10025-33 peptide-pulsed DC vaccination with administration of the anti-IL-10 mAb.
Results:
Vaccination with human gp10025-33 peptide-pulsed DC was the most effective immunization protocol, although not achieving a full protection. Administration of the anti-IL-10 mAb showed also a remarkable protective effect, replicated in mice challenged with a different tumor, Anaplastic Large Cell Lymphoma. When immunization with gp10025-33 peptide-pulsed DC was associated with IL-10 counteraction, a 100% protective effect was consistently achieved. The analysis on the T-cell tumor infiltrates showed an increase of CD4+granzyme+ T-cells and a decreased number of CD4+CD25+Foxp3+ Treg elements from mice treated with either gp10025-33 peptide-pulsed DC vaccination or anti-IL-10 mAb administration. These data suggest that processes of intratumoral re-balance between effector and regulatory T cell subpopulations may play a critical protective role in immunotherapy protocols.
Conclusions:
Here we demonstrate that, in the setting of a cancer vaccine strategy, a comparative analysis of different personalized approaches may favour the unveiling of the most effective protocol. Moreover, our findings suggest that counteraction of IL-10 activity may be critical to revert the intratumoral environment promoting Treg polarization, thus increasing the effects of a vaccination against selected TAA.
Insights
Combining gp100 peptide-pulsed dendritic cell (DC) vaccination with anti-interleukin-10 (IL-10) antibody treatment achieved 100% protection against experimental melanoma. This strategy rebalances tumor-infiltrating T-cells, enhancing cancer vaccine efficacy.
Area of Science:
- Immunology
- Oncology
- Vaccinology
Background:
- Cancer vaccines show promise but have limited clinical success.
- Ineffective tumor-associated antigen selection and immunization protocols hinder robust cancer vaccine design.
- Systematic analysis is crucial for identifying optimal tumor-associated antigens and vaccination strategies.
Purpose of the Study:
- To compare different gp100 vaccination strategies for experimental melanoma.
- To identify the most effective strategy for achieving complete and reproducible protection.
- To investigate the role of IL-10 in the tumor microenvironment and its impact on vaccine efficacy.
Main Methods:
- Mice were vaccinated with gp100 peptide, gene, or peptide-pulsed dendritic cells (DCs).
- Anti-interleukin-10 (IL-10) monoclonal antibody (mAb) was administered to counteract regulatory cells.
- Combinatorial treatment involved gp100 peptide-pulsed DC vaccination and anti-IL-10 mAb administration.
Main Results:
- Human gp100 peptide-pulsed DC vaccination was effective but not fully protective.
- Anti-IL-10 mAb administration demonstrated significant protective effects against melanoma and lymphoma.
- Combining gp100 peptide-pulsed DC vaccination with anti-IL-10 mAb achieved 100% protection.
- Treatment modulated T-cell infiltrates, increasing effector CD4+granzyme+ T-cells and decreasing regulatory CD4+CD25+Foxp3+ T-cells.
Conclusions:
- Comparative analysis of personalized cancer vaccine approaches can reveal optimal protocols.
- Counteracting IL-10 activity is critical for reversing the intratumoral environment and enhancing vaccine effects.
- Rebalancing effector and regulatory T-cell subpopulations is key for successful cancer immunotherapy.
