About

Begonya Comin-Anduix is a professor in the Pharmacology Department at the University of California, Los Angeles. Her research focus is on cancer immunotherapy and the use of radioligands for theranostics. She is particularly interested in how the immune system interacts with radioligands used to treat certain types of cancers. These radioligands are made by coupling radioactive particles to molecules capable of recognizing tumor antigens, such as antibodies or immune T cell receptor fractions. Her work explores the dual function of these theranostic agents as highly specific non-invasive imaging molecules and therapeutic agents targeting tumor cells. Her research involves the deep characterization of how these therapies affect tumor immunobiology and other immune organs, as well as investigating resistance mechanisms used by tumors in pre-clinical and clinical settings. She is also dedicated to optimizing, validating, and applying immune monitoring methods at the single-cell level in translational environments. Her efforts aim to enhance T cell responses to metastatic melanoma, renal cell carcinoma, sarcoma, and prostate cancer through immune monitoring, establishing objective and quantitative assays to monitor activation status of cancer-specific T, NK, and dendritic cells. This work seeks to identify parameters that predict treatment outcomes and better understand the tumor microenvironment. Additionally, Begonya Comin-Anduix focuses on the optimization and production of transgenic cellular products under current good manufacturing practice (cGMP) for immunotherapy in cancer clinical trials. She has collaborated in producing transgenic dendritic cells for renal cell carcinomas and in the manufacturing of transgenic stem cells and T cells for adoptive cell transfer for sarcomas.

Research topics

• Immunology
• Computational biology
• Medicine
• Biology
• Internal medicine
• Cancer research

Selected publications

• Abstract No. 564 Porcine-Based Platform for Image-Guided Delivery of Allogeneic Natural Killer Cell Immunotherapy

  Journal of Vascular and Interventional Radiology · 2026-03-23

  article
  PublisherDOI

• Overcoming myeloid-driven resistance to CAR T therapy by targeting SPP1

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-03 · 3 citations

  preprintOpen access

  Chimeric antigen receptor CAR T cell therapy faces notable limitations in treatment of solid tumors. The suppressive tumor microenvironment TME, characterized by complex interactions among immune and stromal cells, is gaining recognition in conferring resistance to CAR T cell therapy. Despite the abundance and diversity of macrophages in the TME, their intricate involvement in modulating responses to CAR T cell therapies remains poorly understood. Here, we conducted single-cell RNA sequencing scRNA seq on tumors from 41 glioma patients undergoing IL13Ra2-targeted CAR T cell therapy, identifying elevated suppressive SPP1 signatures predominantly in macrophages from patients who were resistant to treatment. Further integrative scRNA seq analysis of high-grade gliomas as well as an interferon-signaling deficient syngeneic mouse model both resistant to CAR T therapy demonstrated the role of congruent suppressive pathways in mediating resistance to CAR T cells and a dominant role for SPP1+ macrophages. SPP1 blockade with an anti-SPP1 antibody abrogates the suppressive TME effects and substantially prolongs survival in IFN signaling-deficient and glioma syngeneic mouse models resistant to CAR T cell therapy. These findings illuminate the role of SPP1+ macrophages in fueling a suppressive TME and driving solid tumor resistance to CAR cell therapies. Targeting SPP1 may serve as a universal strategy to reprogram immune dynamics in solid tumors mitigating resistance to CAR T therapies.

  PublisherOA PDFDOI

• TMIC-42. CONQUERING SPP1+ MYELOID-DRIVEN RESISTANCE OF GLIOBLASTOMA TO IL13RA2-TARGETED CAR T CELL THERAPY

  Neuro-Oncology · 2024-11-01 · 2 citations

  articleOpen access

  Abstract In the evolving landscape of glioblastoma (GBM) therapy, the recent proliferation of clinical trials exploring chimeric antigen receptor (CAR) T cell interventions has garnered attention, although their therapeutic efficacy remains limited. Despite recent progress in elucidating the role of the GBM microenvironment in immunotherapy resistance, particularly regarding intercellular networks and macrophages, significant ambiguities endure, impeding a comprehensive understanding of resistance mechanisms amidst the patient-specific heterogeneity of the tumor microenvironment (TME). In this study, we utilized single-cell RNA sequencing to analyze tumors from 41 glioma patients undergoing IL13Rα2-targeted CAR T cell therapy. Our findings unveiled heightened suppressive extracellular network signatures, particularly SPP-1, predominantly observed within myeloid cells from non-responsive patients. The clinical significance of both SPP1+ myeloid cell abundance and overall expression levels revealed associations with patient outcomes. Subsequently, transcriptomic insights were translated to myeloid cell functions in patients exhibiting high versus low SPP1 expression. SPP1-expressing macrophages displayed diminished antigen presentation, phagocytosis, and cell-mediated cytotoxicity, along with augmented extracellular matrix biogenesis and degradation, iron efflux, and suppressive interleukin pathways. Moreover, SPP1-high macrophages exhibited enhanced ligand-receptor interactions, implying a predisposition towards suppressive activities. Immunometabolism pathways, including lipid and ketone body biogenesis and regeneration, were upregulated in SPP1-expressing macrophages, indicating an increased reliance on non-glycolysis-mediated ATP production. To assess translational implications, the therapeutic efficacy of SPP1 blockade was evaluated in a syngeneic glioma model. Blockade of SPP1 with an anti-SPP1 antibody prior to CAR T cell infusion effectively mitigated the immunosuppressive milieu, reversing resistance in preclinical GBM models to murine IL13Rα2-targeted CAR T cell therapy. Subsequent profiling of tumors post-treatment provided insights into TME alterations following SPP1 blockade therapy. This investigation illuminates the intricate interplay between the TME and CAR T cell therapy resistance in GBM, underscoring SPP1 as a promising therapeutic target to surmount CAR T cell resistance and enhance treatment outcomes.

  PublisherOA PDFDOI

• Pigs as Clinically Relevant Models for Synergizing Interventional Oncology and Immunotherapy

  Journal of Vascular and Interventional Radiology · 2024-01-21 · 8 citations

  articleOpen access

  Traditionally, rodent cancer models have driven pre-clinical oncology research. However, they do not fully recapitulate characteristics of human cancers, and their size poses challenges when evaluating tools in the interventional oncologists’ armamentarium. Pig models, however, have been the gold standard for validating surgical procedures. Their size enables the study of image-guided interventions using human US, CT, and MRI platforms. Furthermore, pigs have immunologic features that are similar to those in humans, which can potentially be leveraged for studying immunotherapy. Novel pig models of cancer are being developed but additional research is required to better understand both the pig immune system and malignancy to enhance the potential for pig models in interventional oncology research. In this review, we will address the main advantages and disadvantages of using a pig model for interventional oncology and outline the specific characteristics of pig models that make them better suited to investigate locoregional therapies. Traditionally, rodent cancer models have driven pre-clinical oncology research. However, they do not fully recapitulate characteristics of human cancers, and their size poses challenges when evaluating tools in the interventional oncologists’ armamentarium. Pig models, however, have been the gold standard for validating surgical procedures. Their size enables the study of image-guided interventions using human US, CT, and MRI platforms. Furthermore, pigs have immunologic features that are similar to those in humans, which can potentially be leveraged for studying immunotherapy. Novel pig models of cancer are being developed but additional research is required to better understand both the pig immune system and malignancy to enhance the potential for pig models in interventional oncology research. In this review, we will address the main advantages and disadvantages of using a pig model for interventional oncology and outline the specific characteristics of pig models that make them better suited to investigate locoregional therapies.

  PublisherDOI

• IL-13Rα2/TGF-<b>β</b> bispecific CAR-T cells counter TGF-<b>β</b>-mediated immune suppression and potentiate anti-tumor responses in glioblastoma

  Neuro-Oncology · 2024 · 52 citations

  • Cancer research
  • Medicine
  • Immunology

  BACKGROUND: Chimeric antigen receptor (CAR)-T cell therapies targeting glioblastoma (GBM)-associated antigens such as interleukin-13 receptor subunit alpha-2 (IL-13Rα2) have achieved limited clinical efficacy to date, in part due to an immunosuppressive tumor microenvironment (TME) characterized by inhibitory molecules such as transforming growth factor-beta (TGF-β). The aim of this study was to engineer more potent GBM-targeting CAR-T cells by countering TGF-β-mediated immune suppression in the TME. METHODS: We engineered a single-chain, bispecific CAR targeting IL-13Rα2 and TGF-β, which programs tumor-specific T cells to convert TGF-β from an immunosuppressant to an immunostimulant. Bispecific IL-13Rα2/TGF-β CAR-T cells were evaluated for efficacy and safety against both patient-derived GBM xenografts and syngeneic models of murine glioma. RESULTS: Treatment with IL-13Rα2/TGF-β CAR-T cells leads to greater T-cell infiltration and reduced suppressive myeloid cell presence in the tumor-bearing brain compared to treatment with conventional IL-13Rα2 CAR-T cells, resulting in improved survival in both patient-derived GBM xenografts and syngeneic models of murine glioma. CONCLUSIONS: Our findings demonstrate that by reprogramming tumor-specific T-cell responses to TGF-β, bispecific IL-13Rα2/TGF-β CAR-T cells resist and remodel the immunosuppressive TME to drive potent anti-tumor responses in GBM.

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• Supplementary Data from IND-Enabling Studies for a Clinical Trial to Genetically Program a Persistent Cancer-Targeted Immune System

  2023-03-31

  preprintOpen access

  &lt;p&gt;Supplemental Figure 1: Hypothetical model of peripheral blood TCR-transgenic cell repopulation. Supplemental Figure 2: GLP team organizational chart. Supplemental Figure 3. Bone marrow transplant (BMT) optimization studies in HLA-A2/Kb transgenic mice. Supplemental Figure 4. Body weight and hematology assessment at day 5 and 3 months after BMT. Supplemental Figure 5. Spleen and bone marrow cellularity at day 5 and 3 months after BMT. Supplemental Figure 6. Serum chemistry at 3 months after BMT. Supplemental Figure 7. Flow cytometry gating strategy for bone marrow and splenocytes phenotype characterization. Supplemental Figure 8. Survival and hematology 3 months after BMT with Lin- cells transduced with LV-empty, LV-NY-ESO-1 TCR or LV-NY-ESO-1 TCR/sr39TK. Supplemental Figure 9. Differentiation of NYESO TCR/sr39TK-engineered T cells in ATOs (artificial thymic organoids). Supplemental Table 1. Certificate of Analysis of the GMP-comparable LV-NY-ESO-1 TCR/sr39TK (RRL-MSCV-optNYESO-optsr39TK-WPRE, production volume: 20L). Supplemental Table 2. Certificate of Analysis of the Clinical Grade Lentivirus LV-NY-ESO- 1 TCR/sr39TK (RRL-MSCV-optNYESO-optsr39TK-WPRE, production volume 60L). Supplemental Table 3. Certificate of Analysis of the clinical grade RV-NY-ESO-1 TCR (MSGV1-A2aB-1G4A-LY3H10) (Production volume 18L)*. Supplemental Table 4. Certificate of Analysis of the GMP comparable RV-NY-ESO-1 TCR (MSGV1-A2ab-1G4A-Ly3H10, Production volume: 3L). Supplemental Table 5. Co-Administration of NY-ESO-1 TCR Genetically Modified T cells and Hematopoietic Stem Cells (HSCs) in HLA-A2.1/Kb mice. GLP studies cohort distribution. Supplemental Table 6. Cell manufacturing acceptance criteria. Supplemental Table 7. List of protocol-specific organs. Supplemental Table 8. Manufacturing validation runs. Supplemental Table 9. Comparison between fresh and cryopreserved product at 1, 30, 90 and 180# days.&lt;/p&gt;

  PublisherDOI

• Supplementary Data from IND-Enabling Studies for a Clinical Trial to Genetically Program a Persistent Cancer-Targeted Immune System

  2023-03-31

  preprintOpen access

  &lt;p&gt;Supplemental Figure 1: Hypothetical model of peripheral blood TCR-transgenic cell repopulation. Supplemental Figure 2: GLP team organizational chart. Supplemental Figure 3. Bone marrow transplant (BMT) optimization studies in HLA-A2/Kb transgenic mice. Supplemental Figure 4. Body weight and hematology assessment at day 5 and 3 months after BMT. Supplemental Figure 5. Spleen and bone marrow cellularity at day 5 and 3 months after BMT. Supplemental Figure 6. Serum chemistry at 3 months after BMT. Supplemental Figure 7. Flow cytometry gating strategy for bone marrow and splenocytes phenotype characterization. Supplemental Figure 8. Survival and hematology 3 months after BMT with Lin- cells transduced with LV-empty, LV-NY-ESO-1 TCR or LV-NY-ESO-1 TCR/sr39TK. Supplemental Figure 9. Differentiation of NYESO TCR/sr39TK-engineered T cells in ATOs (artificial thymic organoids). Supplemental Table 1. Certificate of Analysis of the GMP-comparable LV-NY-ESO-1 TCR/sr39TK (RRL-MSCV-optNYESO-optsr39TK-WPRE, production volume: 20L). Supplemental Table 2. Certificate of Analysis of the Clinical Grade Lentivirus LV-NY-ESO- 1 TCR/sr39TK (RRL-MSCV-optNYESO-optsr39TK-WPRE, production volume 60L). Supplemental Table 3. Certificate of Analysis of the clinical grade RV-NY-ESO-1 TCR (MSGV1-A2aB-1G4A-LY3H10) (Production volume 18L)*. Supplemental Table 4. Certificate of Analysis of the GMP comparable RV-NY-ESO-1 TCR (MSGV1-A2ab-1G4A-Ly3H10, Production volume: 3L). Supplemental Table 5. Co-Administration of NY-ESO-1 TCR Genetically Modified T cells and Hematopoietic Stem Cells (HSCs) in HLA-A2.1/Kb mice. GLP studies cohort distribution. Supplemental Table 6. Cell manufacturing acceptance criteria. Supplemental Table 7. List of protocol-specific organs. Supplemental Table 8. Manufacturing validation runs. Supplemental Table 9. Comparison between fresh and cryopreserved product at 1, 30, 90 and 180# days.&lt;/p&gt;

  PublisherOA PDFDOI

• Data from Effects of MAPK and PI3K Pathways on PD-L1 Expression in Melanoma

  2023-03-31

  preprintOpen access

  &lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; PD-L1 is the main ligand for the immune inhibitory receptor PD-1. This ligand is frequently expressed by melanoma cells. In this study, we investigated whether PD-L1 expression is controlled by melanoma driver mutations and modified by oncogenic signaling inhibition.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; Expression of PD-L1 was investigated in a panel of 51 melanoma cell lines containing different oncogenic mutations, including cell lines with innate and acquired resistance to BRAF inhibitors (BRAFi). The effects of targeted therapy drugs on expression of PD-L1 by melanoma cells were investigated.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; No association was found between the level of PD-L1 expression and mutations in &lt;i&gt;BRAF&lt;/i&gt;, &lt;i&gt;NRAS&lt;/i&gt;, &lt;i&gt;PTEN&lt;/i&gt;, or amplification of &lt;i&gt;AKT&lt;/i&gt;. Resistance to vemurafenib due to the activation of alternative signaling pathways was accompanied with the induction of PD-L1 expression, whereas the resistance due to the reactivation of the MAPK pathway had no effect on PD-L1 expression. In melanoma cell lines, the effects of BRAF, MEK, and PI3K inhibitors on expression of PD-L1 were variable from reduction to induction, particularly in the presence of INFγ. In PD-L1–exposed lymphocytes, vemurafenib paradoxically restored activity of the MAPK pathway and increased the secretion of cytokines.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; In melanoma cell lines, including BRAFi-resistant cells, PD-L1 expression is variably regulated by oncogenic signaling pathways. PD-L1–exposed lymphocytes decrease MAPK signaling, which is corrected by exposure to vemurafenib, providing potential benefits of combining this drug with immunotherapies. &lt;i&gt;Clin Cancer Res; 20(13); 3446–57. ©2014 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;

  PublisherDOI

• Abstract 510: Targeting metabolic vulnerabilities to reduce triple negative breast cancer health disparities

  Cancer Research · 2023-04-04

  article

  Abstract Triple negative breast cancer (TNBC) occurs in 10-15% of all breast cancer (BC) patients, yet it accounts for almost half of all BC deaths. Women of African ancestry (WAA) are twice as likely as women of European Ancestry (WEA) to be diagnosed with advanced TNBC with worse prognosis. Emerging data shows that insulin resistance and high circulating levels of insulin are more prevalent in WAA with invasive BCs than in WEA, and activation of the AKT/mTOR pathway by insulin may occur in aggressive TNBC. Reports show diabetic patients treated with metformin, a biguanide drug used to treat diabetes type 2, have reduced incidence of BC and improved survival. However, anticancer actions of metformin require use of high drug doses with limiting side effects in vivo. To address this challenge, we used a structure-activity strategy to develop biguanide analogues with more potent anticancer action and safety at lower doses in vivo. Using TNBC cell proliferation in vitro to screen analogues, promising candidates were identified that exerted dose-dependent inhibition of cell proliferation at significantly lower doses than that of parental metformin (P&amp;lt;0.01). As antitumor effects of metformin are attributed in part to activation of LKB1-AMPK pathways, we find that biguanide analogues also strongly induce AMPK phosphorylation on Western immunoblots and significantly reduce phosphorylation of downstream mTOR signaling pathway components including p70S6K, S6 ribosomal protein and 4E-BP1. Further, analogues induce TNBC cell apoptosis in vitro at lower doses than metformin. In vivo, analogues were more effective than metformin in stopping human TNBC xenograft progression in nude mouse models (P&amp;lt;0.001). Notably, analogues were also more effective than metformin at blocking lung metastases in syngeneic murine 4T1 TNBC models (P&amp;lt;0.05). Transcriptome analyses comparing mammary tumors and lung metastases revealed that analogue JD006 down-regulated genes related to oxidative phosphorylation in lung metastases treated with JD006 and increased expression of genes related to T-cell activation. Further, gene expression in tumors treated with JD006 showed significant down-regulation of long non-coding RNAs that associate with the up-regulation of malignant transformation and activation of M1 macrophages. Importantly, our data indicate that analogue JD006 modulates the activity/trafficking of myeloid-derived suppressor cells (MDSC) and tumor infiltrating lymphocytes (TIL) that may significantly impact TNBC responses to immune checkpoint inhibitors. Further understating of potential biologic differences between TNBC of WAA and WEA is needed to design more effective therapeutic strategies to reduce TNBC health disparities. New targeted treatments could be beneficial for patients afflicted with this deadly disease. (Funding: CBCRP B27IB3869, 4IB-0058; NCI U54 CA143930; JCCC BC Award, Team Research Grant; UCLA TDG). Citation Format: Diana C. Márquez-Garban, Gang Deng, Lorena P. Burton, Gaoyuan Ma, Vishaka Muhunthan, Begonya Comin-Anduix, Gabriela Llarena, Neda Moatamed, Jennifer Murphy, Nalo Hamilton, Daivd Shackelford, Michael E. Jung, Richard J. Pietras. Targeting metabolic vulnerabilities to reduce triple negative breast cancer health disparities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 510.

  PublisherDOI

• Data from Intra–Lymph Node Prime-Boost Vaccination against Melan A and Tyrosinase for the Treatment of Metastatic Melanoma: Results of a Phase 1 Clinical Trial

  2023-03-31

  preprintOpen access

  &lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; The goal of this study was to test the safety and activity of a therapeutic vaccine, MKC1106-MT, in patients with metastatic melanoma.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; MKC1106-MT comprises a plasmid (pMEL-TYR) and two peptides (E-MEL and E-TYR), corresponding to Melan A and tyrosinase, administered by intra–lymph node injection in a prime-boost sequence. All 18 patients were HLA-A*0201 positive and received a fixed priming dose of plasmid and a low or a high peptide dose. Enumeration of antigen-specific T cells was done prior to and throughout the treatment. Patients who did not exhibit disease progression remained on study and could receive up to eight cycles of treatment.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; The MKC1106-MT regimen was well tolerated and resulted in an overall immune response rate of 50%. The treatment showed disease control, defined as stable disease that lasted for 8 weeks or more in 6 of 18 (33%) of the patients: 14% and 46% in the low and high peptide dose, respectively. Interestingly, four patients, all with tumor burden largely confined to lymph nodes and Melan A–specific T cells at baseline, showed durable disease control associated with radiologic evidence of tumor regression. There was no noticeable correlation between the expansion of antigen-specific T cells in blood and the clinical outcome; yet, there was evidence of active tumor-infiltrating lymphocytes (TIL) in two regressing lesions.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; MKC1106-MT showed immunogenicity and evidence of disease control in a defined patient population. These findings support further development of this investigational agent and the concept of therapeutic vaccination in metastatic melanoma. &lt;i&gt;Clin Cancer Res; 17(9); 2987–96. ©2011 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;

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Frequent coauthors

• Antoni Ribas

  Parker Institute for Cancer Immunotherapy

  170 shared

• Richard C. Koya

  75 shared

• Thinle Chodon

  Roswell Park Comprehensive Cancer Center

  64 shared

• Thomas G. Graeber

  52 shared

• Owen N. Witte

  52 shared

• James S. Economou

  University of California, Los Angeles

  46 shared

• Alistair J. Cochran

  University of California, Los Angeles

  43 shared

• James R. Heath

  Institute for Systems Biology

  42 shared