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Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Vaccination with CD47 deficient tumor cells elicits an antitumor immune response in mice
Yang Li1,2, Mingyou Zhang1,2, Xiaodan Wang1,3
1Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital, and Institute of Immunology, Jilin University, Changchun, China.
Abstract:
Cancer cells are poorly immunogenic and have a wide range of mutations, which makes them unsuitable for use in vaccination treatment. Here, we show that elimination of CD47, a ligand for the myeloid cell inhibitory receptor SIRPα, from tumor cells by genetic deletion or antibody blocking, significantly improves the effectiveness of the immune response to tumour cells. In both solid and hematopoietic mouse tumor models, vaccination with tumor cells or tumor antigen-expressing cells, that lack CD47 or were pre-coated with anti-CD47 antibodies, achieved an antitumor immune response. The efficacy of this approach was synergistically enhanced when used in combination with anti-PD-1 antibodies. The induction of antitumor responses depends on SIRPα+CD11c+ DCs, which exhibit rapid expansion following introduction of CD47-deficient tumor cells. Our results indicate that CD47-deficient whole tumor cells can induce antitumor responses.
Insights
Eliminating CD47 from cancer cells enhances immune responses for vaccination. Combining CD47-deficient tumor cells with anti-PD-1 antibodies synergistically boosts antitumor immunity.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Cancer cells often evade immune detection due to poor immunogenicity and high mutation rates.
- Current cancer vaccination strategies face challenges in eliciting effective antitumor immune responses.
Purpose of the Study:
- To investigate the impact of CD47 elimination on the immunogenicity of tumor cells.
- To evaluate the efficacy of CD47-deficient tumor cell vaccination in established cancer models.
- To explore combination therapies involving CD47 blockade and immune checkpoint inhibitors.
Main Methods:
- Genetic deletion or antibody-mediated blocking of CD47 on mouse tumor cells.
- Vaccination of tumor-bearing mice with CD47-deficient tumor cells or antigen-expressing cells.
- Assessment of antitumor immune responses, including T cell activation and DC expansion.
- Combination therapy with anti-PD-1 antibodies.
Main Results:
- Elimination of CD47 significantly enhanced the immune response against tumor cells in both solid and hematopoietic mouse models.
- Vaccination with CD47-deficient tumor cells induced a robust antitumor immune response.
- The combination of CD47-deficient tumor cells and anti-PD-1 antibodies resulted in synergistic enhancement of efficacy.
- CD47-deficient tumor cells promoted the expansion of SIRPα+CD11c+ dendritic cells, crucial for initiating antitumor immunity.
Conclusions:
- CD47-deficient whole tumor cells can effectively induce antitumor immune responses.
- Targeting CD47 represents a promising strategy to overcome tumor-induced immune suppression.
- Combination therapy with CD47 blockade and PD-1 inhibitors offers a synergistic approach for cancer immunotherapy.
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