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A Personalized Cancer Vaccine that Induces Synergistic Innate and Adaptive Immune Responses
Da-Sol Kuen1, Jihye Hong2, Suyoung Lee1
1Laboratory of Immune Regulation, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, 08826, Seoul, Republic of Korea.
Abstract:
To demonstrate potent efficacy, a cancer vaccine needs to activate both innate and adaptive immune cells. Personalized cancer vaccine strategies often require the identification of patient-specific neoantigens; however, the clonal and mutational heterogeneity of cancer cells presents inherent challenges. Here, extracellular nanovesicles derived from alpha-galactosylceramide-conjugated autologous acute myeloid leukemia (AML) cells (ECNV-αGC) are presented as a personalized therapeutic vaccine that activates both innate and adaptive immune responses, bypassing the need to identify patient-specific neoantigens. ECNV-αGC vaccination directly engages with and activates both invariant natural killer T (iNKT) cells and leukemia-specific CD8+ T cells in mice with AML, thereby promoting long-term anti-leukemic immune memory. ECNV-αGC sufficiently serves as an antigen-presenting platform that can directly activate antigen-specific CD8+ T cells even in the absence of dendritic cells, thereby demonstrating a multifaceted cellular mechanism of immune activation. Moreover, ECNV-αGC vaccination results in a significantly lower AML burden and higher percentage of leukemia-free survivors among cytarabine-treated hosts with AML. Human AML-derived ECNV-αGCs activate iNKT cells in both healthy individuals and patients with AML regardless of responsiveness to conventional therapies. Together, autologous AML-derived ECNV-αGCs may be a promising personalized therapeutic vaccine that efficiently establishes AML-specific long-term immunity without requiring the identification of neoantigens.
Insights
Extracellular nanovesicles from acute myeloid leukemia (AML) cells activate innate and adaptive immunity, offering a personalized cancer vaccine. This approach bypasses neoantigen identification, reducing AML burden and improving survival.
Area of Science:
- Immunology
- Oncology
- Nanotechnology
Background:
- Effective cancer vaccines require activation of both innate and adaptive immune cells.
- Personalized cancer vaccines face challenges due to cancer cell heterogeneity and the need for neoantigen identification.
- Current therapeutic strategies for acute myeloid leukemia (AML) have limitations.
Purpose of the Study:
- To present extracellular nanovesicles derived from alpha-galactosylceramide-conjugated autologous AML cells (ECNV-αGC) as a personalized therapeutic vaccine.
- To demonstrate that ECNV-αGC activates both innate and adaptive immune responses without neoantigen identification.
- To evaluate the efficacy of ECNV-αGC in reducing AML burden and improving survival in mice.
Main Methods:
- Development of ECNV-αGC from autologous AML cells conjugated with alpha-galactosylceramide.
- In vivo studies in mice with AML to assess immune cell activation (iNKT cells and CD8+ T cells) and anti-leukemic effects.
- Evaluation of ECNV-αGC's antigen-presenting capabilities and activation of iNKT cells in human samples.
Main Results:
- ECNV-αGC vaccination activated both invariant natural killer T (iNKT) cells and leukemia-specific CD8+ T cells in mice with AML, promoting long-term immune memory.
- ECNV-αGC acted as an antigen-presenting platform, directly activating antigen-specific CD8+ T cells independently of dendritic cells.
- Vaccination with ECNV-αGC significantly reduced AML burden and increased leukemia-free survival in cytarabine-treated mice.
- Human AML-derived ECNV-αGCs activated iNKT cells in healthy individuals and AML patients, irrespective of prior treatment response.
Conclusions:
- Autologous AML-derived ECNV-αGCs represent a promising personalized therapeutic vaccine strategy for AML.
- This approach efficiently establishes AML-specific long-term immunity by activating innate and adaptive immune responses.
- ECNV-αGC bypasses the need for neoantigen identification, simplifying personalized cancer vaccine development.
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