About

Kristopher R. Bosse, MD, is an Assistant Professor of Pediatrics (Oncology) at the University of Pennsylvania School of Medicine. He is an attending physician in the Division of Oncology at the Children's Hospital of Philadelphia and a member of the Abramson Cancer Center and the Center for Cellular Immunotherapies at the University of Pennsylvania. His professional focus includes pediatric oncology, with particular expertise in neuroblastoma and other high-risk pediatric cancers. Dr. Bosse's work involves developing and applying innovative immunotherapeutic strategies, including CAR T cell therapies, to treat pediatric cancers. His research aims to enhance the efficacy and safety of cellular immunotherapies, contributing to advancements in targeted cancer treatments for children.

Research topics

• Biology
• Computational biology
• Genetics
• Cancer research
• Immunology
• Bioinformatics

Selected publications

• Abstract 6169: Evaluating TCR mimetic CAR T cell preclinical therapeutics in an immunocompetent MYCN-driven murine neuroblastoma allograft model

  Cancer Research · 2026-04-03

  article

  Abstract Background: Tractable immunocompetent murine models for adoptive cellular therapies could fill a critical gap in preclinical evaluations. Peptide-centric (PC) chimeric antigen receptor (CAR) T cells targeting pMHC of a 9mer peptide derived from the neuroblastoma intracellular oncoprotein PHOX2B presented by HLA-A*24:02 (A24) is now in Phase 1 clinical trial for relapsed neuroblastoma (NCT07007117). To study therapeutic limitations and enhancement strategies, we developed a syngeneic model of PHOX2B/A24-targeting murine (m)PC-CARs. Methods: C57BL/6 (BL/6)-penetrant TH-MYCN-derived allografts and cell lines were engineered with a chimeric human/murine MHC HLA-A*24:02/H-2Kb to present conserved PHOX2B 9mer peptide. MSCV retroviral vectors encoding second-generation mPC-CARs containing the clinical scFv conjoined to murine CD28 or 4-1BB with CD3ζ were used to create stable GPE86 producer cell lines. Truncated mCD19 or luciferase was included to monitor transduction efficiency and in vivo trafficking. BL/6 splenocytes were activated and transduced ex vivo with human (h)IL-2, and expanded in hIL-7/15. Multiplex functional assays were performed using flow cytometry, ELISA, real-time cell impedance, and O-link proteomics. Results: Transduction efficiency reproducibly ranged from 40-60%. mPC-CAR-T cells expanded 15 to 20-fold over 14 days while maintaining balanced memory and effector immunophenotypes with minimal exhaustion markers post-manufacture. Against PHOX2B-A24-H-2Kb-expressing cell lines, mPC-CAR-T cells with CD28ζ or 4-1BBζ costimulatory domains exhibited robust IFN-γ, IL-2, and TNFα secretion and potent cytotoxicity down to an effector:target ratio of 0.5:1 up to 14 days post-manufacture and after cryopreservation. CD28ζ mPC-CAR T cells maintained 100% cytotoxicity upon serial tumor rechallenge, whereas cytotoxicity of 4-1BBζ was limited to 50% after 3 challenges. In the absence of exogenous cytokine support, tumor exposure induced CD44+IL7Rα- terminal effector phenotype and upregulation of exhaustion markers CD39, CTLA-4, and Tim-3. In vivo studies to assess anti-tumor potency, persistence, and barriers to efficacy are ongoing and will be reported. Conclusion: We created a tractable MHC hybrid TH-MYCN-derived neuroblastoma allograft model in BL/6 mice. This model is currently being deployed to study various PC-CAR enhancement strategies such as mRNA encoded epitope vaccination and cytokine armoring with accompanying spatial transcriptomics that will inform further clinical development of our PHOX2B-directed PC-CAR T cells. Citation Format: Elisabeth Posthill, Minu Samanta, David Groff, Colleen Casey, Tina Acholla, Anna Maria Giudice, Kristopher R. Bosse, Ruoning Wang, Timothy T. Spear, John M. Maris. Evaluating TCR mimetic CAR T cell preclinical therapeutics in an immunocompetent MYCN-driven murine neuroblastoma allograft model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6169.

  PublisherDOI

• Abstract 7809: Epitope-encoded mRNA-LNP vaccine to enhance anti-tumor potency and persistence of PHOX2B peptide-centric CAR T cells

  Cancer Research · 2026-04-03

  article

  Abstract Background: A Phase 1/1b clinical trial testing peptide-centric chimeric antigen receptor (PC-CAR) T cells that recognize a peptide derived from the major neuroblastoma oncoprotein PHOX2B presented in the context of HLA-A*24:02 and 20 other HLA-A alleles is showing early signs of safety and efficacy (NCT07007117). Anticipated barriers to durable cures include poor persistence and a hostile tumor immune microenvironment (TIME). We hypothesize that persistence and potency can be enhanced, without compromising safety, through the deployment of a “CAR boosting” PHOX2B epitope-encoding mRNA-lipid nanoparticle (LNP) vaccine. Methods: We established a screening platform to test various PHOX2B mRNAs and LNP designs, and here report on the prioritized formulation: a nucleoside-modified PHOX2B 9mer monomer encapsulated by FDA-approved LNP SM-102. In parallel, we established a genetically engineered mouse model (GEMM) of NB to deploy our PHOX2B epitope mRNA-LNP vaccination strategy in vivo. Results: A24+ healthy donor or NB patient monocyte-derived dendritic cells (moDCs) treated with vaccine exhibited log-fold higher PHOX2B 9mer presentation compared to tumor cells and upregulated T cell costimulatory ligands CD80/86 and CD40. PC-CAR T cells exposed to vaccine-treated moDCs had significantly increased proliferation, polyfunctionality, and migratory markers compared to co-cultures with HLA matched NB cell lines. Moreover, vaccine-treated moDCs enriched central, effector, and/or stem cell memory PC-CAR T cell immunophenotypes (donor/patient-dependent) compared to tumor-induced PD1hiCD39hi terminal effectors. PC-CAR T cells primed with vaccine-treated moDCs maintained significantly greater cytotoxicity in serial tumor rechallenges. A comprehensive characterization of the immunobiological effects of mRNA-LNP on DC and PC-CAR T cell function using O-link proteomics and transcriptional profiling are ongoing and will be reported. GEMM-derived allografts faithfully recapitulate human disease and express a chimeric HLA-A*24:02/H-2Kb MHC that presents a conserved PHOX2B 9mer. Murine (m)PC-CAR T cells engineered with clinical scFv conjoined to murine 41BB- or CD28-CD3ζ were polyfunctional and cytotoxic against A24/H-2Kb allografts. Vaccine-treated A24/H-2Kb knock-in mice presented PHOX2B 9mer by DCs in spleen and lymph nodes, activating PC-CAR T cells. Comprehensive in vivo evaluation of mPC-CAR-T expansion, memory formation, and anti-tumor potency with TIME spatialomic profiling are ongoing and will be reported. Conclusion: These IND-enabling studies will inform our clinical vaccine dosing strategy with the recommended Phase 2 PC-CAR T cell dose in an upcoming trial amendment. This CAR boosting vaccine may not only improve efficacy of PC-CAR T cells for NB but also guide mRNA-LNP enhancement strategies for other adoptive cellular therapies. Citation Format: Timothy T. Spear, Nicholas Hartnett, Elisabeth Posthill, David Groff, Dana Al-Halawani, Minu Samanta, Keelan O'Reilly, Richa Kapoor, Muzamil Want, Lingling Liu, Tingting Wang, Ruoning Wang, Richard Madnick, Irina Shkundina, Kristopher R. Bosse, Mohamad-Gabriel Alameh, Drew Weissman, John M. Maris. Epitope-encoded mRNA-LNP vaccine to enhance anti-tumor potency and persistence of PHOX2B peptide-centric CAR T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7809.

  PublisherDOI

• Abstract 4027: Co-targeting GPC2 and B7-H3 with CAR T cells achieves durable responses in preclinical high-risk neuroblastoma and medulloblastoma models

  Cancer Research · 2026-04-03

  articleSenior author

  Abstract Glypican 2 (GPC2) is highly expressed in pediatric cancers including high-risk neuroblastomas and medulloblastomas, and GPC2 CAR T cells are now in phase 1 trials (NCT05650749, NCT07087002). However, durable responses are limited by heterogeneous antigen expression, treatment-induced antigen loss, and poor CAR T persistence. In neuroblastoma, interconvertible adrenergic (ADRN) and mesenchymal (MES) states further complicate targeting, as state switching downregulates GPC2 and GD2, whereas B7-H3 remains consistently expressed. B7-H3 is also abundant across other GPC2+ cancers, supporting a dual GPC2.B7-H3 CAR strategy. To approach GPC2.B7-H3 dual CAR T cell targeting, we engineered seven GPC2/B7-H3 co-targeting bicistronic CAR constructs containing CD28, 4-1BB, or OX40 costimulatory domains and either two (dual, d1-3) or one (parallel, p1-4) CD3-ζ signaling domain. Among these, d1 and p2 were prioritized because they drove strong activation of Jurkat NFAT-GFP CAR T cells in co-cultures with isogenic NALM-6 cells expressing either or both antigens and showed superior cytokine secretion in human CAR T co-incubation assays compared with single-antigen B7-H3 (B) or GPC2 (G) CARs. In vivo, dual-targeting CAR T cells - double-transduced (B/G) or expressing d1 or p2 - achieved potent clearance of COG-N-453x neuroblastoma PDXs, with 16-week cure rates of 83.3%, 83.3%, and 100%, exceeding single CARs (B, 57.1%; G, 0%). Human CAR T cell persistence was detected in bone marrow and spleen of cured mice at 16 weeks, suggesting a role of enhanced T cell persistence in durable remissions. In the aggressive COG-N-561x model, only bicistronic CARs d1 and p2 achieved durable 14-15-week cures (d1, 100%; p2, 71.4%), surpassing double-transduced (B/G, 33.3%), co-administered (B+G, 20%), or single CARs (B, 20%; G, 0%). Upon rechallenge, only d1 and p2 cohorts rejected tumors and remained tumor-free long-term (d1, 71.4%; p2, 60%), again with persistent CAR T cells in bone marrow and spleen through the 36-week study endpoint. Finally, across in vitro medulloblastoma models, repeat tumor-stimulation assays confirmed superior activity of d1 and p2. In an aggressive orthotopic group 3 medulloblastoma 7316-10374 xenograft model where 100% of GPC2 CAR-treated mice relapsed, the p2 CAR outperformed d1 and the single B7-H3 CAR, with 16-week cure rates of 100%, 71.4%, and 60%, respectively, confirming the superiority of dual GPC2.B7-H3 targeting and a potential advantage of parallel CD3ζ-sharing designs. Altogether, GPC2.B7-H3 bicistronic CARs induced durable and curative responses across neuroblastoma and medulloblastoma models, nominating this approach as a next-generation GPC2 CAR T strategy for clinical testing. Citation Format: Patrick M. Schürch, Benjamin Draper, Vincent P. Zecchino, Hehai Pan, Brandi Nelson, Anna M. Giudice, Jessica B. Foster, Laura K. Donovan, Kristopher R. Bosse. Co-targeting GPC2 and B7-H3 with CAR T cells achieves durable responses in preclinical high-risk neuroblastoma and medulloblastoma models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4027.

  PublisherDOI

• Identification of CD74-positive antigen presenting glioma cells in primary human tumors and murine models of NF1 high-grade glioma

  Molecular Cancer Therapeutics · 2026-04-02 · 1 citations

  article

  Compared to the general population, individuals with Neurofibromatosis Type 1 have a 50-fold higher risk of developing a high-grade glioma (HGG) in their lifetime. Despite improved understanding of the molecular and cellular drivers of these neoplasms, we have yet to translate this knowledge into therapies that improve overall survival. One limitation has been the paucity of in vivo models for drug testing within this population. We generated 3 distinct glioma stem cell lines from high-grade gliomas arising in mice with Nf1 and Trp53 mutations in cis (NPcis) and characterized the allografts resulting from one Nf1-glioma stem cell line (Nf1-HGG17) by single cell and single nuclear RNA-seq. Because our cell lines are grown in stem cell media, there is an inherent reduction of the differentiation states present in primary HGG, with only oligodendrocyte precursor-like and neural-like cells identified. However, orthotopic allografts of Nf1-HGG17 regained the other differentiation states typically observed in HGG and GBM (neuronal progenitor cell-like and astrocyte-like). About half of neoplastic cells cluster separately from these classical groups and highly express genes of the antigen presentation machinery, including Cd74, which we also observed in patient samples. Notably, heterozygosity of Nf1 within the tumor microenvironment does not cause marked changes in the immune tumor microenvironment, gene expression, or differentiation states of neoplastic cells. These data indicate that allografted HGG lines from NPcis mice are an effective model of NF1-HGG, mimicking the complexity observed in human HGG, that can be used for larger scale in vivo drug screening and evaluation.

  PublisherDOI

• IL1RAP antibody-drug conjugates potently target primary and metastatic disease in multiple oncofusion-driven cancers

  Cancer Discovery · 2026-04-13

  articleOpen access

  Gene fusions generated by chromosomal rearrangements function as oncogenic drivers in human cancers. We previously showed that EWSR1-ETS oncofusions of Ewing sarcoma (EwS) directly induce surface expression of IL1 receptor accessory protein (IL1RAP), which along with limited expression in healthy tissues except placenta nominate IL1RAP as a promising EwS immunotherapy target. We therefore engineered antibody-drug conjugates (ADCs) with different cytotoxic payloads to target IL1RAP. ADCs potently blocked tumor growth and induced durable regression of EwS xenografts in mice, and diminished metastatic dissemination in vivo. Moreover, we show that other oncofusions also induce IL1RAP expression in diverse cancers, including NPM-ALK in anaplastic large cell lymphoma (ALCL), and ETV6-NTRK3 in multiple tumor types. IL1RAP expression rendered these malignancies similarly vulnerable to IL1RAP-targeting ADCs, which effectively blocked growth of ALCL xenografts and syngeneic ETV6-NTRK3+ sarcomas. Lack of detectable normal tissue toxicity, including in non-human primates, support the further clinical translation of IL1RAP-targeting ADCs.

  PublisherDOI

• Abstract 1332: Selective targeting of the α3β4 nicotinic acetylcholine receptor by DISCO (dual interacting subunit complex) CAR T cells.

  Cancer Research · 2026-04-03

  articleSenior author

  Abstract Developing effective chimeric antigen receptor (CAR) T cell therapies for pediatric solid tumors requires discovery of highly tumor-selective cell surface molecules. Using a multimodal immunotherapeutic target discovery platform, we identified a receptor composed of the nicotinic acetylcholine receptor subunits α3 and β4 as a new previously unrecognized immunotherapeutic target in neuroblastoma. CHRNA3 (α3) and CHRNB4 (β4) are robustly differentially overexpressed in neuroblastoma compared with normal tissues, driven by a super-enhancer upstream of the CHRNA3/B4 locus on chromosome 15q25 that is occupied by neuroblastoma core regulatory transcription factors and physically engages both promoters. Neuroblastoma cells exhibit abundant α3 and β4 protein, which bind and assemble into a stabilized α3β4 complex displayed at high levels on the neuroblastoma cell surface. Functionally, genetic depletion of α3 also reduced β4 levels, induced mesenchymal cell state-associated marker expression, and increased proliferation and invasion in neuroblastoma cell line models. To therapeutically exploit this tumor-restricted α3β4 receptor expression, we engineered Dual Interacting Subunit COmplex (DISCO)-specific single chain variable fragments (scFvs) designed to recognize an epitope requiring simultaneous engagement of both α3 and β4 subunits of the α3β4 cell surface receptor. DISCO CAR T cells generated from these scFvs bound selectively to and were potently activated by the α3β4 receptor, but not either subunit individually. α3β4-targeted DISCO CAR T cells demonstrated potent and selective cytotoxicity across diverse neuroblastoma cell lines and three patient-derived xenograft (PDXs) models, significantly extending the survival of mice harboring PDXs with a range of α3 and β4 expression (P < 0.05). Beyond neuroblastoma, CHRNA3 and CHRNB4 are also highly expressed in small cell lung cancer (SCLC) and retinoblastoma, among several other tumors. The identical super-enhancer is associated with high levels of CHRNA3 and CHRNB4 in SCLC, suggesting similar mechanisms of tumor-driven overexpression. In an intraocular retinoblastoma xenograft model, a single intravitreal dose of α3β4-redirected DISCO CAR T cells achieved marked tumor control and significantly extended ocular survival (P = 0.0015), collectively showing disease-relevance and targetability beyond neuroblastoma. Together, these findings broaden the repertoire of actionable CAR T cell targets in pediatric and adult solid tumors by validating the α3β4 receptor, and more broadly the nicotinic acetylcholine receptor family, as bona fide immunotherapeutic candidates. Moreover, these studies demonstrate that CARs can be designed to recognize disease-relevant subunit configurations within multidomain surface receptors. Citation Format: Patrick M. Schürch, Vincent P. Zecchino, Anna M. Giudice, Rebecca S. Kaufman, Evan Cresswell-Clay, Guillem Pascual-Pasto, Sydney L. Roth, Brendan C. McIntyre, Rawan Shraim, Amber K. Hamilton, Kush Parikh, Karina L. Conkrite, Khanh B. Trang, Grant P. Grothusen, David Groff, Pamela Mishra, Simona Lombardi, Tyler Skinner, Andrew D. Wells, Struan F. Grant, Daniel Martinez, Wei Li, Sharon J. Diskin, Kristopher R. Bosse. Selective targeting of the α3β4 nicotinic acetylcholine receptor by DISCO (dual interacting subunit complex) CAR T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1332.

  PublisherDOI

• Supplementary Figure S6 from D3-GPC2–Directed CAR T Cells Are Safe and Efficacious in Preclinical Models of Neuroblastoma and Small Cell Lung Cancer

  2025-12-15

  articleOpen accessSenior author

  <p>GPC2-expressing SCLCs activate and are susceptible to D3-GPC2 CAR T cell killing from a second T cell donor.</p>

  PublisherOA PDFDOI

• Supplementary Figure S3 from D3-GPC2–Directed CAR T Cells Are Safe and Efficacious in Preclinical Models of Neuroblastoma and Small Cell Lung Cancer

  2025-12-15

  articleOpen accessSenior author

  <p>D3-GPC2 CAR-28z T cells are robustly and selectively cytotoxic to GPC2-expressing neuroblastoma cells.</p>

  PublisherOA PDFDOI

• Scratching the surface of targeting GPC2 on pediatric CNS tumors

  Molecular Therapy Oncology · 2025-12-01

  articleOpen accessSenior author
  PublisherDOI

• Data from D3-GPC2–Directed CAR T Cells Are Safe and Efficacious in Preclinical Models of Neuroblastoma and Small Cell Lung Cancer

  2025-12-15

  articleOpen accessSenior author

  <div>AbstractPurpose:<p>We previously identified glypican 2 (GPC2) as a cell-surface MYCN-regulated neuroblastoma oncoprotein and developed a D3-GPC2 antibody that specifically binds a conformational, tumor-specific epitope conserved between mouse and human.</p>Experimental Design:<p>In this study, we sought to further validate GPC2 as an immunotherapeutic target and develop Investigational New Drug application–enabling data to support the clinical translation of D3-GPC2 chimeric antigen receptor (CAR) T cells.</p>Results:<p>Immunohistochemistry validated that GPC2 is widely expressed on human neuroblastomas, and flow cytometry showed high levels of cell-surface GPC2 on neuroblastoma cellular models. Second-generation D3-GPC2 CAR T cells with either a 4-1BB or CD28 co-stimulatory domain were selectively activated and induced potent neuroblastoma cell cytotoxicity in several complementary <i>in vitro</i> co-incubation assays. Conversely, no measurable cytotoxicity or D3-GPC2 CAR T-cell activation was observed in co-incubation studies with nine primary human normal tissue cell lines. Moreover, GPC2 CAR T cells induced significant regression of GPC2-expressing neuroblastoma xenografts. No GPC2 CAR-related toxicities were noted, including in comprehensive mouse necropsies performed after GPC2 CAR T-cell administration. Finally, to explore the potential broader clinical impact of GPC2 CAR T cells, we showed that they are also potently cytotoxic to preclinical models of GPC2-expressing small cell lung cancers.</p>Conclusions:<p>These data validate GPC2 as a <i>bona fide</i> CAR T-cell target in neuroblastoma and other cancers. The safety and preliminary efficacy of GPC2 CAR T cells are being tested in a first-in-human phase I clinical trial for children with relapsed/refractory neuroblastoma (NCT05650749).</p></div>

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Recent grants

• Targeting the GPC2 oncoprotein with immune-based therapies in neuroblastoma

  NIH · $1.0M · 2018–2023

Frequent coauthors

• John M. Maris

  226 shared

• Sharon J. Diskin

  Children's Hospital of Philadelphia

  123 shared

• Håkon Håkonarson

  University of Pennsylvania

  95 shared

• Maura Diamond

  Children's Hospital of Philadelphia

  83 shared

• Yaël P. Mossé

  University of Pennsylvania

  81 shared

• Mario Capasso

  80 shared

• Marcella Devoto

  National Research Council

  75 shared

• Bruce Pawel

  65 shared

Education

• MD, Perelman School of Medicine

  University of Pennsylvania

  2010

• AB

  Bowdoin College

  2002