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SIR 2025

General IR

Scientific Session

Session: Interventional Oncology 1

Novel Method for Assessing Tumor Humoral Responses After Image-Guided Percutaneous Treatments

Sunday, March 30, 2025
3:45 PM – 3:54 PM CT
Location: Music City Center, 208 AB
Purpose: Image-guided interventional radiology (IR) treatments like transarterial therapies and percutaneous ablations cause tumor cell lysis and release of intracellular antigens to prime anti-tumor immune responses that can synergize with systemic therapies {1}. Immune response quantification after IR treatments has focused on cellular (T cell) immunity, but knowledge of humoral (B cell) immunity in this context is lacking. Tumor infiltrating B cells (TIL-Bs) support tumor T cell development, produce anti-tumor antibodies (Abs), are associated with improved survival in many cancers, and thus are critical for effective anti-tumor immunity {2-5}. Therefore, the purpose of this study was to establish a novel strategy for isolation and characterization of functional anti-tumor Abs.

Materials and Methods: As proof-of-concept for establishing a pipeline to investigate tumor B cell responses and isolate anti-tumor Abs elicited after IR treatments; we performed single cell transcriptome and B cell receptor (BCR) sequencing of TIL-Bs enriched from non-small cell lung cancer (NSCLC) tumors that were readily available to our lab. Diverse TIL-B populations were annotated using reference B cell gene libraries. We then combined our transcriptome and BCR sequencing data to probe various B cell subsets for candidate tumor-reactive Abs, allowing us to generate recombinant monoclonal Abs (mAbs) that were tested for binding and effector functions.

Results: We identified eight TIL-B populations highlighting differentiation of tumor B cells, indicative of active tumor immunity. Focusing on Ab-secreting plasma cells, we produced 20 mAbs thus far, 14 of which bound strongly to tumor antigens found on the cell surface as demonstrated by ELISA and immunofluorescent staining of NSCLC cell lines and their lysates. Combining immunoprecipitation of tumor cell line lysates with mass spectrometry, we identified cell surface-expressed tumor proteins as targets bound by our lead tumor-reactive mAb candidate (“Ab4”). To assess therapeutic potential of our tumor mAbs, we generated CAR-T cells bearing the Ab4 binding domain and demonstrated killing of diverse tumor cell lines, suggesting these novel mAbs can be developed into therapeutics.

Conclusion: We established a high-throughput pipeline for isolation of novel tumor Abs and discovery of tumor antigens that may be used to inform the design of novel Ab-based cancer therapeutics and vaccines. Our pipeline may enhance the capability for efficient identification of locoregional therapy factors that can optimally synergize with systemic immunotherapies.