- |||||||||| CTX130 / CRISPR Therap, CTX131 / CRISPR Therap
Journal, CAR T-Cell Therapy, Metastases: CD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced Clear Cell Renal Cell Carcinoma. (Pubmed Central) - Apr 7, 2024
Although the role of CAR T cells is well established in hematologic malignancies, the clinical experience in solid tumors has been disappointing. This clinical trial demonstrates the first complete response in a patient with RCC, reinforcing the potential benefit of CAR T cells in the treatment of solid tumors.
- |||||||||| Unleashing CAR T cell activity against osteosarcoma using tumor specific RNA-based vaccination (Section 40) - Mar 5, 2024 - Abstract #AACR2024AACR_7733;
RNA-NPs in combination with CAR T cells prolong long-term survival of mice bearing these aggressive tumor models which was not only mediated by CAR T cells but also by activation of endogenous adaptive immunity. Future studies include the evaluation of this approach in large animal models prior to translation into first-in-human clinical trials.
- |||||||||| CD70-specific CAR-T cell therapy for the treatment of glioblastoma (Section 2) - Mar 5, 2024 - Abstract #AACR2024AACR_2823;
In conclusion, we provide evidence in favor of utilization of CAR-T cells against CD70-expressing gliomas. Based on these findings, a phase-I clinical trial to assess the safety and efficacy of autologous CD70-specific CAR-T cells for relapsed CD70+ GB is being planned.
- |||||||||| 8R-70CAR T / University of Florida
CD70 CXCR2-Modified CAR T-Cells Against Acute Myeloid Leukemia () - Dec 11, 2023 - Abstract #TCTASTCTCIBMTR2024TCT_ASTCT_CIBMTR_901;
P1
A LLS tumoroid model can aid in 3D visualization of 8R-70CAR T cells interactions AML cells. These findings combined with safety data obtained from our ongoing phase I clinical trial for adults with glioblastoma (NCT05353530) will support expansion of our existing IND to treat patients with AML using our novel 8R-70CAR.
- |||||||||| Journal, CAR T-Cell Therapy, IO biomarker: Bioconjugated Liquid-Like Solid Enhances Characterization of Solid Tumor - Chimeric Antigen Receptor T Cell Interactions. (Pubmed Central) - Nov 27, 2023
To better study these specialized CAR T cells in this context, we have developed an innovative in vitro three-dimensional model that promises to dissect the interactions between tumors and CAR T cells at the single-cell level. Our findings provide valuable insights into the complex dynamics of CAR T cell function in solid tumors, informing future research and development in this promising cancer treatment approach.
- |||||||||| azacitidine / Generic mfg.
Discovery and Development of CD70 As a Cellular Therapy Target in High Risk Multiple Myeloma (SDCC - Room 6A) - Nov 3, 2023 - Abstract #ASH2023ASH_3085;
Taken together, targeting CD70 appears to be a highly promising cellular therapeutic strategy for MM, with particularly high utility in high-risk patients after BCMA CAR-T relapse. We are continuing preclinical and future clinical development of this CAR-T strategy, using our natural ligand CD27 design with extended in vivo persistence.
- |||||||||| Journal: Rabies virus glycoprotein 29 (RVG29) promotes CAR-T immunotherapy for glioma. (Pubmed Central) - Oct 23, 2023
RVG modification enables CAR-T cells to cross the BBB, and stimulation with glioma cells induces 70R CAR-T cells to expand in a resting state. The modification of RVG29 has a positive impact on CAR-T therapy for brain tumors and may have potential in CAR-T therapy for glioma.
- |||||||||| OUTLAST (Exhibit Hall B) - Oct 19, 2023 - Abstract #SITC2023SITC_1821;
suppression and 5) superior control of tumor cells in vivo in an aggressive repeat challenge model. Conclusions Overall, we show that OTX CD70 CAR-T cells exhibit multiple attributes desired of CAR-T cells for effective and superior function in the solid tumor microenvironment, and that they
- |||||||||| 8R-70CAR T / University of Florida
Enrollment open, Trial completion date, Trial primary completion date, CAR T-Cell Therapy: Phase I Study of IL-8 Receptor-modified CD70 CAR T Cell Therapy in CD70+ Adult Glioblastoma (IMPACT) (clinicaltrials.gov) - Jul 31, 2023
P1, N=18, Recruiting,
Conclusions Overall, we show that OTX CD70 CAR-T cells exhibit multiple attributes desired of CAR-T cells for effective and superior function in the solid tumor microenvironment, and that they Not yet recruiting --> Recruiting | Trial completion date: Dec 2041 --> Dec 2042 | Trial primary completion date: Dec 2026 --> Dec 2027
- |||||||||| CD70 HIT T cells overcome tumor antigen heterogeneity in renal cell carcinoma (Valencia BC - Convention Center) - Mar 14, 2023 - Abstract #AACR2023AACR_3170;
This represents a significant advance for the development of a potentially effective cellular therapy for RCC, which may be applicable to other aggressive CD70-positive tumors like ovarian and pancreatic cancers. Our findings underscore the critical importance of assessing antigen expression in a quantitative manner to determine if antigens are truly absent or present at very low levels, in which case they may be responsive to an engineered antigen-sensitive immune cell as afforded by the HIT receptor.
- |||||||||| Pozenveo (poziotinib) / Spectrum Pharma, Luye Group, Tagrisso (osimertinib) / AstraZeneca
CD70-targeting CAR-T and CAR-NK cells demonstrate potent activity against NSCLC drug-tolerant persister cells (Section 37; Poster Board #6) - Mar 14, 2023 - Abstract #AACR2023AACR_2272;
Furthermore, we determined that CD70-targeting CAR-T and CAR-NK cells showed promising in vitro activity against the DTPCs of osimertinib-treated EGFR mutant NSCLC. These results demonstrate CAR-based cellular therapy as an effective approach to target DTPCs and identify CD70 as a novel therapeutic target for combatting DTPCs in NSCLC.
- |||||||||| Preclinical, Journal, CAR T-Cell Therapy, IO biomarker: Preclinical evaluation of CD70-specific CAR T cells targeting acute myeloid leukemia. (Pubmed Central) - Mar 3, 2023
Our study reveals that anti-CD70 CAR-T cells are a new potential treatment for AML. However, such CAR-T cell therapy did not completely eliminate leukemia in vivo, suggesting that future studies aiming to generate innovative combinatorial CAR constructs or to increase CD70 expression density on leukemia cell surface to prolong the life-span of CAR-T cells in the circulation will be needed in order to optimize CAR-T cell responses for AML.
- |||||||||| Journal: CD70 is a therapeutic target upregulated in EMT-associated EGFR tyrosine kinase inhibitor resistance. (Pubmed Central) - Feb 14, 2023
However, such CAR-T cell therapy did not completely eliminate leukemia in vivo, suggesting that future studies aiming to generate innovative combinatorial CAR constructs or to increase CD70 expression density on leukemia cell surface to prolong the life-span of CAR-T cells in the circulation will be needed in order to optimize CAR-T cell responses for AML. Anti-CD70 antibody drug conjugates (ADCs) and CD70-targeting chimeric antigen receptor (CAR) T
- |||||||||| Developing CD70-Targeted CAR-T Cells for the Treatment of Hematological and Solid Malignancies () - Nov 29, 2022 - Abstract #ASH2022ASH_7776;
Furthermore, the CD70 CAR T cells displayed potent anti-tumor activities, as evident by in vitro killing against CD70 expressed cell lines, such as Molm-13, an AML cell line, or ACHN, a RCC cell line; and by in vivo tumor inhibition and clearance in immunodeficient xenograft mouse model. Together, our data support the further development of CD70-targeted CAR-T cells for the treatment of hematological and solid malignancies.
- |||||||||| Novel cellular therapies to achieve cures in clear cell renal cell carcinoma () - Oct 8, 2022 - Abstract #KCRS2022KCRS_68;
Impact and Innovation: Building on our long-term research of developing ccRCC cellular therapy, we anticipate filing an Investigational New Drug application and advancing second-generation DFIR-CAR T to clinic after completion of these studies. Significant scientific advances will be made to overcome the barriers that have prevented this promising "living drug" therapy to be developed for patients with advanced ccRCC and to deliver safe and effective therapy.
- |||||||||| Identification of novel immune checkpoint molecule in glioma, LAIR1 (West/Central Hall) - Sep 28, 2022 - Abstract #SNO2022SNO_677;
Significant scientific advances will be made to overcome the barriers that have prevented this promising "living drug" therapy to be developed for patients with advanced ccRCC and to deliver safe and effective therapy. This study suggests that we identified a novel immune checkpoint molecule, LAIR1, which can limit tumor progression.
- |||||||||| Journal: Enhancement of CD70-specific CAR T treatment by IFN-γ released from oHSV-1-infected glioblastoma. (Pubmed Central) - Sep 14, 2022
More importantly, combined therapy generated potent antitumor efficacy, increased the proportion of T cells and natural killer cells in TME, and reduced regulatory T cells and transformed growth factor-β1 expression in orthotopic xenotransplanted animal model of GBM. In summary, we reveal that oHSV-1 enhance the therapeutic efficacy of CD70-spefific CAR T cells by intratumoral T cell infiltration and IFN-γ release, supporting the use of CAR T therapy in GBM therapeutic strategies.
- |||||||||| Journal, CAR T-Cell Therapy: CD70 CAR T cells in AML: Form follows function. (Pubmed Central) - May 26, 2022
Using a multimodal approach toward developing a new CD70-targeted Chimeric antigen receptor (CAR) T cell in acute myeloid leukemia, Leick et al. report on their synergetic strategy, which incorporates both CAR T cell construct modifications with enhancement of leukemia antigen expression to improve CAR T cell functionality.
- |||||||||| CD70-directed CAR-T / Massachusetts General Hospital
Journal, CAR T-Cell Therapy: Non-cleavable hinge enhances avidity and expansion of CAR-T cells for acute myeloid leukemia. (Pubmed Central) - May 15, 2022
Our CD8 hinge and transmembrane-modified CD70 CAR-T cells are less prone to cleavage, have enhanced binding avidity, and increased expansion, leading to more potent in vivo activity. This enhanced CD70-targeted CAR is a promising candidate for further clinical development.
- |||||||||| Tagrisso (osimertinib) / AstraZeneca
CD70 is a novel therapeutic target for EGFR mutant NSCLC with acquired, EMT-associated EGFR TKI resistance (Section 23) - Mar 9, 2022 - Abstract #AACR2022AACR_6788;
CD70-targeting approaches including anti-CD70 antibody drug conjugates (ADCs) and CD70-targeting CAR T cell and CAR NK cells showed promising in vitro and in vivo activity against CD70 positive tumor cells and in osimertinib drug-tolerant persister cells. These results identify CD70 as a novel therapeutic target for EGFR mutant tumors with acquired EGFR TKI resistance that merits further investigation in the clinic.
- |||||||||| Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Preclinical development and evaluation of allogeneic CAR T cells targeting CD70 for the treatment of renal cell carcinoma (Section 18) - Mar 9, 2022 - Abstract #AACR2022AACR_2483;
CD70 CAR T cells were evaluated with rituximab-based off switches to provide control over CAR T function and displayed robust antitumor activity against RCC cell lines and patient-derived xenografts in mouse models...Lastly, highly functional CD70 allogeneic CAR T cells were produced at large scale through elimination of the T cell receptor by TALEN® gene editing. Taken together, these efficacy and safety data support the evaluation of CD70 CAR T cells for the treatment of RCC and led to the advancement of an allogeneic CD70 CAR T candidate into Phase I clinical trials.
- |||||||||| Journal, CAR T-Cell Therapy, IO biomarker: CD70-specific CAR T cells have potent activity against acute myeloid leukemia without HSC toxicity. (Pubmed Central) - Dec 16, 2021
Although CD70-CAR T cells recognized activated virus-specific T cells (VSTs) that expressed CD70, they did not prevent colony formation by normal hematopoietic stem cells. Thus, CD70-targeted immunotherapy is a promising new treatment strategy for patients with CD70-positive AML that does not affect normal hematopoiesis but will require monitoring of virus-specific T-cell responses.
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