About

Vijay G Bhoj, MD PhD, is an Assistant Professor of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania within the Department of Pathology and Laboratory Medicine. His clinical expertise is in transfusion medicine, which includes therapeutic apheresis and blood banking. His research focuses on cellular immunotherapy, conducting translational research that spans preclinical development of immunotherapies to patient correlative studies and phase I clinical trials. He primarily concentrates on using engineered cells for immune modulation and treatment of non-malignant conditions such as autoimmunity and transplantation. His ongoing projects involve immune Thrombotic Thrombocytopenic Purpura (iTTP), Type 1 Diabetes (T1D), multiple sclerosis (MS), Systemic Lupus Erythematosus (SLE), Hemophilia A, and organ transplantation, utilizing in vitro, murine, and non-human primate models. Additionally, he has played a leading role in studies related to immunity in the context of CAR T cell therapy and vaccination, and he serves in an advisory capacity on mechanistic studies related to phase I CAR T cell trials for medullary thyroid carcinoma and desensitization strategies in highly allosensitized kidney transplant candidates.

Research topics

• Immunology
• Biology
• Internal medicine
• Medicine
• Gastroenterology
• Cell biology
• Cancer research
• Pathology

Selected publications

• Data repository: Spatial atlas of diabetic kidney disease reveals a B cell-rich subgroup

  Zenodo (CERN European Organization for Nuclear Research) · 2026-04-29

  datasetOpen access

  Data repository linked to our manuscript including annotated CosMx 1k and Xenium 5k atlas in anndata format. Please also see the separate diagnosis file for sample information.

  PublisherDOI

• Engineered extracellular vesicles displaying bi-specific T-cell engagers for targeted therapy of B-cell malignancies

  Experimental Hematology and Oncology · 2026-02-07

  articleOpen access

  Despite the clinical success of T cell-based immunotherapies such as CAR-T cells and bispecific T cell engagers (BiTEs), therapeutic resistance and immune suppression remain significant barriers in B-cell malignancies. To address these, we developed a novel dual-functional extracellular vesicle (EV) platform, termed BiTE EV@STA, that displays anti-CD3/CD19 BiTE molecules on the EV surface while encapsulating a STING agonist (STA). This strategy enables simultaneous redirection of cytotoxic T cells to tumor cells and stimulation of innate immunity within the tumor microenvironment (TME). BiTE EVs demonstrated favorable pharmacokinetics, enhanced tumor targeting, and robust T cell dependent cytotoxicity and cytokine release. In Nalm6-Luc xenograft models, BiTE EVs significantly inhibited tumor progression and prolonged survival. Further loading of STING agonists into EVs (BiTE EV@STA) activated dendritic cells, and enhanced CD8⁺ T cell infiltration in the TME. Notably, BiTE EV@STA achieved a 4-fold increase in tumor growth inhibition and a marked survival benefit compared to either component alone. This study presents BiTE EV@STA as a promising EV-based immunotherapy that integrates adaptive and innate immune activation to overcome TME-mediated resistance. These findings may have broad implications for enhancing T cell-based therapies in hematologic malignancies and beyond.

  PublisherDOI

• CD4+ T cells mediate CAR-T cell-associated immune-related adverse events after BCMA CAR-T cell therapy

  Nature Medicine · 2026-01-15 · 2 citations

  articleOpen access
  PublisherOA PDFDOI

• Spatial atlas of diabetic kidney disease reveals a B cell-rich subgroup

  Nature · 2026-04-29

  article
  PublisherDOI

• Data repository

  Zenodo (CERN European Organization for Nuclear Research) · 2026-05-01

  datasetOpen access

  Data repository linked to our manuscript including annotated CosMx 1k and Xenium 5k atlas in anndata format. Please also see the separate diagnosis file for sample information. Due to a mistake a version 3 has been created: https://zenodo.org/records/19868428

  PublisherDOI

• Data repository

  Open MIND · 2026-01-01

  dataset

  Data repository linked to our manuscript including annotated CosMx 1k and Xenium 5k atlas in anndata format and the raw adata objects. Please also see the separate diagnosis file for sample information.

• Chimeric antigen receptor T cells against the IGHV4-34 B cell receptor specifically eliminate neoplastic and autoimmune B cells

  Science Translational Medicine · 2026-02-04 · 6 citations

  article

  Current US Food and Drug Administration–approved chimeric antigen receptor (CAR) T cell therapies for B cell leukemias and lymphomas target CD19, which is widely expressed across the B cell lineage, often leading to on-target, off-tumor B cell depletion, prolonged immune suppression, and antigen-negative escape in a subset of patients. In contrast, B cell receptor (BcR) signaling is essential for the survival of most mature B cell neoplasms, and BcRs carrying the immunoglobulin heavy variable gene IGHV4-34 are highly enriched in B cell malignancies compared with normal B cells. Further, self-reactive IGHV4-34 + serum autoantibodies are enriched in aggressive systemic lupus erythematosus (SLE) and other autoimmune diseases. Here, we developed CAR T cells targeting the BcR carrying IGHV4-34 (CART4-34). We found that CART4-34 showed specific cytotoxicity and cytokine secretion toward IGHV4-34 + malignant B cells. In addition, although CD19 was down-regulated upon relapse after treatment with CART19, IGHV4-34 + BcR levels remained intact upon relapse after treatment with CART4-34, suggesting reduced risk of antigen-negative escape. In IGHV4-34 + HBL1 cell line–derived xenograft mouse models, CART4-34 showed robust expansion and antitumor activity comparable to those of CART19. Optimized CAR:BcR binding using shorter CAR hinge domains improved immune synapse morphology and in vivo activity. In addition, we showed that CART4-34 could target human IGHV4-34 + SLE B cells and deplete IGHV4-34 + autoantibodies ex vivo, without targeting healthy B cells or affecting total IgG titers. In conclusion, we developed a CAR T cell product that specifically targets pathogenic B cells in lymphoid malignancies and SLE, offering potential for precision cell therapy for these indications.

  PublisherDOI

• Manufacturing of CRISPR-edited primary mouse CAR T cells for cancer immunotherapy

  Nature Protocols · 2025-07-25 · 5 citations

  review
  PublisherDOI

• Chimeric antigen receptor T-cell therapy in patients with coexisting malignancy and autoimmune disease

  Blood · 2025-11-03

  articleOpen access

  Abstract Background: Chimeric antigen receptor (CART) therapies targeting CD19 or BCMA have shown great potential for treating autoimmune diseases (AD) in early-phase trials by depleting autoreactive B cells and plasma cells, resetting immune tolerance. While these findings suggest efficacy, current clinical evidence is limited to small, selected cohorts. We conducted a real-world analysis of patients (pts) with coexisting AD and relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL) or multiple myeloma (MM) treated with commercial CART19 or BCMA-CART. Methods: We studied 601 pts with r/r B-NHL or MM treated with commercial CART19 or BCMA-CART from 01/2018 to 12/2024 ( data cutoff: June 2025) at our institution. Antitumor responses were evaluated by Lugano criteria (NHL) and IMWG criteria (MM), and adverse events by ASTCT guidelines. AD was defined as active in the presence of serological markers and need for therapy. AD responses were based on symptom improvement and reduced immunosuppression; flares were defined as new/worsening symptoms or increased treatment need. Serum autoantibody profiling (Chang; Nat Commun. 2021) was performed on paired samples from 90 pts (51 CART19, 39 BCMA-CART) at day 0 and month 3 (M3) post-CART. Results: Overall, 403 (67%) pts had B-NHL and 198 (33%) MM. Median follow-up was 26 months. Forty-nine pts (8.2%) had a history of AD (36 with B-NHL; 13 with MM). ADs included rheumatoid arthritis (RA, n=12), autoimmune hemolytic anemia (AIHA) or immune thrombocytopenic purpura (n=9), sarcoidosis (n=9), systemic lupus erythematosus (SLE) or undifferentiated connective tissue disease (n=7), autoimmune thyroid disease (n=4), and inflammatory bowel disease (IBD, n=4). Less common ADs included psoriasis (n=2) and one case each of type 1 diabetes, ankylosing spondylitis, Sjogren's syndrome, uveitis, polymyalgia rheumatica, and autoimmune colitis. Four pts had multiple ADs. AD was more common in females (AD: 57% vs 35%, p<0.01). Within B-NHL and MM cohorts, baseline characteristics (age, histology, CART product, prior lines, transplant history) were similar between AD and non-AD groups.We first evaluated antitumor efficacy and safety of CART19 and BCMA-CART in patients with and without AD. Response rates, progression-free survival, overall survival, and incidence and severity of cytokine release syndrome and neurotoxicity were comparable (p>0.05).We then assessed the impact of CART on AD. Among 49 pts with AD, 2 B-NHL patients (4%)—1 with RA (RA#1) and 1 with SLE (SLE#1)—had active AD at CART19 infusion. Both were symptomatic and on treatment at CART infusion. RA#1 remained in AD remission until death from lymphoma progression 2.5 years post-CART. SLE#1 had a baseline ANA titer of 1:20,000, which decreased to 1:2,500 at M3 post-CART, accompanied by reduced DNA-associated antibodies (anti-histones, KU, P70/80, H2B, H2A/4, H3, H1, nucleolin; median fold change [FC] −70%, range −39% to −84%). In contrast, anti-Smith remained stable (FC −6%) while anti-SSB increased (FC +39%), suggesting selective depletion of pathogenic B-cell clones. SLE#1 experienced SLE relapse 2.3 years post-CART with isolated cutaneous involvement, while in remission of B-NHL.We then evaluated the 47 pts with AD in remission at the time of CART infusion. While 41 (87%) pts maintained AD remission, 6 (13%) pts (3 RA, 1 psoriasis, 1 IBD, and 1 AIHA) experienced AD flares within 3 months post-CART. All resolved with appropriate therapy: corticosteroids (n=2,RA), non-steroidal anti-inflammatory (n=1, RA), topical steroids plus phototherapy (psoriasis), mesalamine (IBD), or red blood cell transfusions (AIHA). To assess the broader impact of CART19 and BCMA-CART on the pt autoreactome (individual-specific autoantibody repertoire; Bodansky; JCI 2024), independently of AD diagnosis, we profiled 90 pts using a bead-based array targeting 52 autoantigens (Chang; Nat Commun. 2021). Both therapies modulated the autoreactome, with BCMA-CART inducing a significantly greater median reduction in autoantibodies (72% vs. 31%, p<0.001), supporting its broader potential in autoantibody-driven diseases. Conclusion: CART confirms durable AD control in real-world pts with coexisting NHL/MM. However, a subset of pts with AD in remission at infusion may experience post-CART AD flares, possibly due to the post-treatment inflammatory state, warranting close monitoring. Further studies are needed to understand flares' pathogenesis and their link with CART activity.

  PublisherOA PDFDOI

• Precision targeting of pathogenic B cells and autoantibodies in systemic lupus erythematosus using CAR T cells against the IGHV4-34 B cell receptor

  Blood · 2025-11-03

  article

  Abstract Introduction: Systemic lupus erythematosus (SLE) is a serious autoimmune disease which chiefly involves B-cell dysregulation and activation, hypergammaglobulinemia, and autoantibody production. Studies have demonstrated that treatment with CART19, a CART targeting CD19, a pan B-cell marker, lead to clinical remissions of SLE. However, broadly targeting B cells with CART19 can lead to B-cell aplasia, hypogammaglobulinemia, and thereby leave patients prone to infections. Of note, in SLE, B cells and autoantibodies expressing the immunoglobulin heavy variable 4-34 (IGHV4-34) gene are highly enriched and associated with SLE severity. Therefore, we hypothesize that CART targeting the IGHV4-34 B-cell receptor (BcR) would preferentially deplete pathogenic B cells without immunosuppression. Methods and Results: To better define the significance of IGHV4-34 BcR as a target, we first aimed to deepen our understanding of how IGHV4-34 immunoglobulins (Ig) contribute to the SLE autoantibody repertoire. We depleted IGHV4-34 Ig from serum and then measured the reduction of specific autoantibodies using a bead-based antigen array. We used sera from SLE patients (n=3), depleted 98-100% of IGHV4-34 Ig, and found a >50% reduction in overall autoantibody levels. Furthermore, we saw reductions of SLE-associated autoantibodies (anti-Ro60, anti-SM, anti-Ribo P0, and anti-DNAse1L3) ranging from 10-100% following IGHV4-34 depletion. Higher levels of IGHV4-34 Ig in the serum have been associated with lupus nephritis (LN). Therefore, we assessed the presence of IGHV4-34+ Ig via immunohistochemistry in 11 randomly selected kidney biopsies from LN patients (5 pediatric LN, 6 adult LN) and 4 controls (1 pediatric C3 glomerulonephritis, 1 pediatric post-streptococcal glomerulonephritis, 2 normal pediatric kidneys). All 13/13 glomerulonephritis biopsies were positive for total IgG, reinforcing the role of immune complexes in nephritis. Remarkably, 10/11 LN biopsies but 0/2 glomerulonephritis controls had IGHV4-34+ antibodies in the affected glomeruli. We, therefore, developed anti-IGHV4-34 CART (CART4-34) using the 9G4 rat monoclonal antibody. Given the large size of the BcR antigen, we optimized CAR:IGHV4-34 immune synapse formation and in vitro and in vivo activity using a shorter CAR hinge domain (G4S hinge [5aa]) instead of the CD8 hinge (44aa). We co-cultured B-cell lines (HBL1, Mec1 WT or IGHV4-34+, Jeko1 WT or IGHV4-34+) with CART4-34 at 0.5-0.25 Effector:Target (E:T) ratios for 48-72hr and observed that CART4-34 exhibits potent activity specifically towards IGHV4-34+ B cells while sparing IGHV4-34-negative B cells (p<0.05). We then developed a model to assess whether CART4-34 could target SLE B cells and reduce autoantibody production. We obtained SLE patient-derived B cells, activated them for 48hr by co-culturing with CpG ODN2006, CD40L, IL2, IL10, and IL15 and differentiated them for 24hr into plasmablasts using IL6, IL2, IL10, and IL15. We then performed a 48hr 0.5 E:T co-culture with CART4-34, CART19, or untransduced T cells. We observed that CART4-34 specifically eliminated IGHV4-34+ B-cells (p=0.005), but not other B cells. Similarly, we measured co-culture total IgG and IGHV4-34+ IgG levels via ELISA and determined that while CART19 significantly depleted all IgG levels (p=0.0004), CART4-34 specifically depleted only IGHV4-34 IgG while simultaneously preserving total IgG. Next, we assessed whether soluble IGHV4-34 Ig could inhibit CART4-34 binding to the target. CART4-34 were co-cultured with HBL1 cells at a 1:1 E:T ratio with 0.1-100ug/ml IGHV4-34+ IgG1 antibody for 72hr. We observed nearly 100% inhibition of CART4-34 function at all Ig concentrations. To overcome this, we hypothesized that Ig depletion, as clinically obtained with plasmapheresis, could restore CART function. Indeed, Ig depletion led to a drastic reduction of the inhibitory effect of the IGHV4-34+ media (p<0.0001). Lastly, to confirm CART4-34 specificity and safety, we conducted next-generation sequencing from normal B-cells cocultured with CART4-34 and controls. CART4-34 led to a statistically significant reduction of only the IGHV4-34 genes out of 46 IGHV genes (p<0.01). Conclusions: These results support our hypothesis that IGHV4-34 Ig plays a role in SLE pathogenesis, particularly in LN. Importantly, CART4-34 can be used to generate potent, targeted, and safe therapy for SLE by targeting IGHV4-34+ B cells, while sparing normal B cells and most of the Ig repertoire.

  PublisherDOI

Frequent coauthors

• Michael C. Milone

  University of Pennsylvania

  42 shared

• Carl H. June

  Parker Institute for Cancer Immunotherapy

  25 shared

• Edmund K. Moon

  21 shared

• Michael D. Feldman

  21 shared

• Liang-Chuan Wang

  21 shared

• Stephen J. Schuster

  University of Pennsylvania

  21 shared

• Enxiu Wang

  21 shared

• Steven Μ. Albelda

  20 shared