In the field of immunological research, identifying and analyzing antigen-specific T cells is crucial. Antigen-specific T cells can specifically recognize and attack pathogens or tumor cells carrying specific antigens, playing a central role in immune responses. Efficient and accurate detection of these antigen-specific T cells is vital for research in tumor immunotherapy.

A single clone of tumor antigen-specific T cells can only specifically recognize one tumor antigen peptide epitope. Tumor cells and tumor antigens exhibit high heterogeneity, with thousands of diverse tumor antigens. Therefore, tumor antigen-specific T cells, capable of specifically recognizing and killing cancer cells, are also diverse, numbering at least in the thousands.

1. Limitations of Using Peptides to Detect Tumor Antigen-Specific T Cells

Currently, to detect tumor antigen-specific T cells, the common method is to synthesize one or more known tumor antigen peptides. These peptides are then co-incubated with T cells to stimulate and activate tumor antigen-specific T cells, followed by flow cytometry to detect markers such as IFN-γ, determining the quantity of tumor antigen-specific T cells. However, using peptides to stimulate tumor antigen-specific T cells has limitations in terms of variety and diversity. The peptides used for T cell stimulation are typically a mixture of several antigen peptides, but with thousands of tumor antigens, it is difficult to synthesize all of them. Therefore, the types of tumor antigen-specific T cells that can be stimulated and detected are limited and not comprehensive. The insufficient diversity of the antigen peptide pool limits the comprehensiveness and accuracy of detecting tumor antigen-specific T cells after peptide stimulation.

2. Advantages of Nanoparticles Loaded with Whole Tumor Cell Antigens in Detecting Tumor Antigen-Specific T Cells

In contrast, nanoparticles loaded with whole tumor cell antigens exhibit significant advantages in detecting tumor antigen-specific T cells. When used, these nanoparticles only need to be co-incubated with a mixture of immune cells containing T cells to activate tumor antigen-specific T cells, allowing for subsequent detection. More importantly, these nanoparticles, due to their load of whole tumor cell antigens, can provide a comprehensive, diverse, and broad spectrum of various tumor antigens, enabling a more thorough and accurate detection of tumor antigen-specific T cells in different tissues such as peripheral blood or lymph nodes. Their advantages include high specificity, strong detection accuracy, and a more comprehensive range of tumor antigen-specific T cells detected.

Recent studies have shown that using nanoparticles loaded with whole tumor cell antigens for co-incubation with immune cell mixtures can detect around 10% of CD8+ IFN-γ+ and CD4+ IFN-γ+ tumor antigen-specific T cells (Figures b and c). In contrast, co-incubating immune cell mixtures with highly immunogenic mixed antigen peptides only detects a small amount of CD8+ IFN-γ+ or CD4+ IFN-γ+ tumor antigen-specific T cells (Figures d and e), significantly less than those detected after stimulation with nanoparticles loaded with whole tumor cell antigens. These data indicate that nanoparticles loaded with whole tumor cell antigens can effectively stimulate and activate a more diverse and broad spectrum of tumor antigen-specific T cells, offering significant advantages in detecting these cells.

Nanoparticles loaded with whole tumor cell antigens provide a more efficient tool for detecting tumor antigen-specific T cells, promising greater utility in predicting therapeutic efficacy and monitoring immunotherapy in the future.

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References

[1] M. Xu, A. Zhu, Y. Pan, Z. Suleman, J. Cheng, M. Liu, PLGA Nanoparticles Coated with Activated Dendritic Cell Membrane Can Prolong Protein Expression and Improve the Efficacy of mRNA. Adv. Therap. 2024, 2400180. https://doi.org/10.1002/adtp.202400180