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Open research questions in CAR-T cell therapy research

327 unresolved questions extracted from the limitations and future-work sections of 816 CAR-T cell therapy research papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Investigating the use of CAR T cell therapy in autoimmune diseases - Exploring the potential of CAR-T cell therapy in fibrotic diseases - Developing HLA-specific CAR-Tregs for transplantation tolerance induction

    CAR T cell therapy beyond cancer: current status, challenges and future prospects · 2026 · DOI

  • Heterogeneous antigen expression in neuroblastoma poses a challenge for targeted immunotherapies. Low MHC class I expression in neuroblastoma limits the effectiveness of TCR-engineered T cell therapy. The need to enhance the cytotoxic activity of TCR T cells against neuroblastoma cells.

    CAR T cell-induced interferon gamma enhances MHC class I expression and sensitizes neuroblastoma to TCR-engineered T cell therapy · 2026 · DOI

  • investigating the efficacy of combining CAR- and TCR-engineered T cells in clinical trials - exploring the potential of other antigens as targets for TCR T cell therapy - studying the effects of IFNγ on MHC class I expression in other types of cancer

    CAR T cell-induced interferon gamma enhances MHC class I expression and sensitizes neuroblastoma to TCR-engineered T cell therapy · 2026 · DOI

  • The complexity of identifying and selecting optimal neoantigens for pTTL therapy. The potential for off-target toxicity and immune-related adverse events. The need for careful patient selection and monitoring to ensure safety and efficacy.

    A first-in-human, phase I/IIa trial of the T cell immunotherapy personalised tumour trained lymphocytes in patients with advanced colorectal cancer: Study protocol · 2026 · DOI

  • Evaluation of biomarkers for pTTL persistence - Assessment of pTTL tumour infiltration - Analysis of the correlation of neoantigen selection to clinical outcome

    A first-in-human, phase I/IIa trial of the T cell immunotherapy personalised tumour trained lymphocytes in patients with advanced colorectal cancer: Study protocol · 2026 · DOI

  • Difficulty in ex vivo immune cell engineering. Limited delivery specificity and high systemic toxicity of traditional delivery systems. Need to overcome biological barriers such as biodistribution, cellular uptake, intracellular transport, and endosomal escape of delivered drugs.

    Targeted delivery platforms for in vivo immune cell engineering: emerging strategies for cancer immunotherapy · 2026 · DOI

  • development of specialized LNPs that allow selective reprogramming of T cells, NK cells, dendritic cells, and other immune cells in vivo, - exploration of biomimetic delivery systems for immune targeting and cancer immunotherapy, - investigation of nanoparticle-based systems for delivery of mRNA, siRNA, plasmids, proteins, and genome editing tools

    Targeted delivery platforms for in vivo immune cell engineering: emerging strategies for cancer immunotherapy · 2026 · DOI

  • The exploratory nature of efficacy-related observations in this phase 1 study - Most participants were heavily pretreated before enrollment, and some pursued additional therapies after study treatment - The use of lymphodepletion in arm C and the associated clinical and biological heterogeneity that may ensue - Interpretation of pooled outcomes of arms B and C is limited

    Multi-antigen-targeting T cells in pediatric central nervous system tumors: a phase 1 trial · 2026 · DOI

  • Further studies to evaluate the efficacy of TAA-T cell therapy in pediatric CNS tumors - Investigation of the optimal dose and administration schedule for TAA-T cell therapy - Research on the mechanisms of clonal expansion and contraction in TAA-T cell therapy

    Multi-antigen-targeting T cells in pediatric central nervous system tumors: a phase 1 trial · 2026 · DOI

  • further study of the mechanisms of long-term CAR T cell persistence, - investigation of the relationship between CAR T cell persistence and clinical outcomes, - analysis of CAR T cell persistence in other types of cancer

    Decade-long persistence of CD19 CAR T cells in B cell lymphomas · 2026 · DOI

  • The extent and biology of long-term CAR T cell persistence in B cell lymphoma remain unclear. The contribution of long-term persistence in B-NHL was less well defined. Small single-center data support that CAR T persistence is associated with prolonged progression-free survival, but more research is needed.

    Decade-long persistence of CD19 CAR T cells in B cell lymphomas · 2026 · DOI

  • more preclinical studies on the effects of IFN-γ on specific elements of the brain microenvironment in ICANS, - investigation of the role of individual cytokines on specific elements of the brain's microstructural environment

    The Mechanisms of Altered Blood–Brain Barrier Permeability in CD19 CAR T–Cell Recipients · 2024 · DOI

  • The exact mechanisms of ICANS development are not fully understood. The role of individual cytokines in the development of ICANS is not well characterized.

    The Mechanisms of Altered Blood–Brain Barrier Permeability in CD19 CAR T–Cell Recipients · 2024 · DOI

  • Although {gamma}{delta} T-cells can detect malignant transformation and exert cytotoxicity, these properties confer potent preclinical efficacy but limited therapeutic activity and the basis for this discrepancy remains unclear.

    Patient-derived ascites reveals functional advantages of γδCAR T-cells within the ovarian cancer-like tumor microenvironment · 2026 · DOI

  • Although γc cytokines are used to expand T cells, their impact on T-cell states remains incompletely defined.

    In Vitro Inhibition of STAT5 Signaling Limits CD8+ T-cell Exhaustion and Improves Outcomes in Adoptive T-cell Therapy · 2026 · DOI

  • Thus, further investigation of this approach, either as a single agent or combined with other complementary modalities, is warranted (ClinicalTrials.

    Autologous multiantigen-targeted T cell therapy for pancreatic cancer: a phase 1/2 trial · 2026 · DOI

  • BACKGROUND AND OBJECTIVES: Neuroimaging findings in immune effector cell-associated neurotoxicity syndrome (ICANS) have not been systematically described.

    Neuroimaging Findings in Children and Young Adults With Neurotoxicity After CAR T-Cell Therapy for B-Cell Malignancies · 2025 · DOI

  • Specific risk factors and short-term and long-term outcomes of ASyS associated with CAR T-cell therapy have not been well investigated.

    Acute Symptomatic Seizures During CAR T-Cell Therapy for Hematologic Malignancies · 2025 · DOI

  • Ultimately, this completed first-in-human trial shows that repetitive ICV dosing of B7-H3 CAR T cells in pediatric and young adult patients with DIPG is tolerable, including multiyear repeated dosing, and may have clinical efficacy that warrants further investigation on a multisite phase 2 trial.

    Intracerebroventricular B7-H3-targeting CAR T cells for diffuse intrinsic pontine glioma: a phase 1 trial · 2025 · DOI

  • Abstract New treatment approaches are warranted for patients with advanced melanoma refractory to immune checkpoint blockade (ICB) or BRAF-targeted therapy.

    Personalized, autologous neoantigen-specific T cell therapy in metastatic melanoma: a phase 1 trial · 2025 · DOI

  • There is limited evidence supporting the feasibility of using omics and functional technologies to inform treatment decisions.

    Feasibility of multiomics tumor profiling for guiding treatment of melanoma · 2025 · DOI

  • This omission represents a significant gap in the literature, with im-plications for global health equity and cancer research prioritization.

    Bridging the gap: cancer scientific equity, global child health, and distribution of CAR T-cell therapy clinical trials in childhood cancer · 2025 · DOI

  • This discrepancy may be partially attributed to T cell immune exhaustion within the tumor microenvironment, although the detailed mechanisms remain unclear.

    Recent Advances in Immunotherapy for Melanoma: Perspectives on the Development of Novel Treatments: A Mini Review · 2025 · DOI

  • Future research will focus on optimizing lymphodepleting regimens, mitigating toxicity, enhancing in vivo persistence, and combining ACT with other therapeutic agents.

    Review of Adoptive Cellular Therapies for the Treatment of Sarcoma · 2025 · DOI

  • There is a lack of detailed analyses on the age-dependent expression of CLDN6 in normal tissues is lacking, which limits the expansion of CLDN6 CAR-T cell clinical trials to pediatric populations.

    The Chimeric Antigen Receptor T Cell Target Claudin 6 Is a Marker for Early Organ-Specific Epithelial Progenitors and Is Expressed in Some Pediatric Solid Tumor Entities · 2025 · DOI

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327 open questions have been extracted from the limitations and future-work passages of 816 CAR-T cell therapy research papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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