Last update 01 Nov 2024

CD3 x TSLPR

Last update 01 Nov 2024

Basic Info

Related Targets

CD3TSLPR

Drugs associated with CD3 x TSLPR

1B7/CD3 BsAb(MD Anderson)

Target

CD3 x TSLPR

Mechanism

CD3 modulators [+1]

Active Org.

The University of Texas MD Anderson Cancer Center

Originator Org.

The University of Texas MD Anderson Cancer Center

Active Indication

Acute Lymphoblastic Leukemia

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CD3 x TSLPR

100 Translational Medicine associated with CD3 x TSLPR

0 Patents (Medical) associated with CD3 x TSLPR

Literatures (Medical) associated with CD3 x TSLPR

01 Jan 2024·Leukemia

Correction: Preclinical development of 1B7/CD3, a novel anti-TSLPR bispecific antibody that targets CRLF2-rearranged Ph-like B-ALL

Author: Gonzalez, Michelle A ; Lofton, Timothy E ; Heffernan, Timothy ; Shi, Qing ; Zhang, Qi ; Chang, Qing ; Olson, Jill Wardell ; Molldrem, Jeffrey J ; Kaur, Jasbir ; Al-Shami, Amin ; Tian, Ze ; Smith, Melinda G ; You, Junping ; Tasian, Sarah K ; Zha, DongXing ; Yang, Guojun ; Jain, Nitin ; Shi, Chunhua ; Konopleva, Marina Y ; Allen, Jason K

Patients harboring CRLF2-rearranged B-lineage acute lymphocytic leukemia (B-ALL) face a 5-yr survival rate as low as 20%.While significant gains have been made to position targeted therapies for B-ALL treatment, continued efforts are needed to develop therapeutic options with improved duration of response.Here, first we have demonstrated that patients with CRLF2-rearranged Ph-like ALL harbor elevated thymic stromal lymphopoietin receptor (TSLPR) expression, which is comparable with CD19.Then we present and evaluate the anti-tumor characteristics of 1B7/CD3, a novel CD3-redirecting bispecific antibody (BsAb) that co-targets TSLPR.In vitro, 1B7/CD3 exhibits optimal binding to both human and cynomolgus CD3 and TSLPR.Further, 1B7/CD3 was shown to induce potent T cell activation and tumor lytic activity in both cell lines and primary B-ALL patient samples.Using humanized cell- or patient-derived xenograft models, 1B7/CD3 treatment was shown to trigger dose-dependent tumor remission or growth inhibition across donors as well as induce T cell activation and expansion.Pharmacokinetic studies in murine models revealed 1B7/CD3 to exhibit a prolonged half-life.Finally, toxicol. studies using cynomolgus monkeys found that the maximum tolerated dose of 1B7/CD3 was ≤1 mg/kg.Overall, our preclin. data provide the framework for the clin. evaluation of 1B7/CD3 in patients with CRLF2-rearranged B-ALL.

01 Oct 2023·Leukemia

Preclinical development of 1B7/CD3, a novel anti-TSLPR bispecific antibody that targets CRLF2-rearranged Ph-like B-ALL

Article

AbstractPatients harboring CRLF2-rearranged B-lineage acute lymphocytic leukemia (B-ALL) face a 5-year survival rate as low as 20%. While significant gains have been made to position targeted therapies for B-ALL treatment, continued efforts are needed to develop therapeutic options with improved duration of response. Here, first we have demonstrated that patients with CRLF2-rearranged Ph-like ALL harbor elevated thymic stromal lymphopoietin receptor (TSLPR) expression, which is comparable with CD19. Then we present and evaluate the anti-tumor characteristics of 1B7/CD3, a novel CD3-redirecting bispecific antibody (BsAb) that co-targets TSLPR. In vitro, 1B7/CD3 exhibits optimal binding to both human and cynomolgus CD3 and TSLPR. Further, 1B7/CD3 was shown to induce potent T cell activation and tumor lytic activity in both cell lines and primary B-ALL patient samples. Using humanized cell- or patient-derived xenograft models, 1B7/CD3 treatment was shown to trigger dose-dependent tumor remission or growth inhibition across donors as well as induce T cell activation and expansion. Pharmacokinetic studies in murine models revealed 1B7/CD3 to exhibit a prolonged half-life. Finally, toxicology studies using cynomolgus monkeys found that the maximum tolerated dose of 1B7/CD3 was ≤1 mg/kg. Overall, our preclinical data provide the framework for the clinical evaluation of 1B7/CD3 in patients with CRLF2-rearranged B-ALL.

28 Jan 2021·BloodQ1 · MEDICINE

Tumor-intrinsic and -extrinsic determinants of response to blinatumomab in adults with B-ALL

Q1 · MEDICINE

Article

Author: Bhatia, Ravi ; Zamora, Anthony E. ; Thomas, Paul G. ; Allen, Emma K. ; Stein, Anthony S. ; Wang, Jeremy ; Gu, Zhaohui ; Marcucci, Guido ; Forman, Stephen J. ; Imamura, Toshihiko ; Mullighan, Charles G. ; Alexander, Thomas B. ; Zhao, Yaqi ; Qu, Chunxu ; Akahane, Koshi ; Crawford, Jeremy Chase ; Aldoss, Ibrahim ; Roberts, Kathryn G. ; Goto, Hiroaki

AbstractBlinatumomab, a bispecific antibody that directs CD3+ T cells to CD19+ tumor cells, shows variable efficacy in B-progenitor acute lymphoblastic leukemia (B-ALL). To determine tumor-intrinsic and -extrinsic determinants of response, we studied 44 adults with relapsed or refractory B-ALL (including 2 minimal residual disease positive) treated with blinatumomab using bulk tumor and single-cell sequencing. The overall response rate in patients with hematological disease was 55%, with a high response rate in those with CRLF2-rearranged Philadelphia chromosome–like ALL (12 [75%] of 16). Pretreatment samples of responders exhibited a tumor-intrinsic transcriptomic signature of heightened immune response. Multiple mechanisms resulted in loss of CD19 expression, including CD19 mutations, CD19-mutant allele-specific expression, low CD19 RNA expression, and mutations in CD19 signaling complex member CD81. Patients with low hypodiploid ALL were prone to CD19− relapse resulting from aneuploidy-mediated loss of the nonmutated CD19 allele. Increased expression of a CD19 isoform with intraexonic splicing of exon 2, CD19 ex2part, at baseline or during therapy was associated with treatment failure. These analyses demonstrate both tumor-intrinsic and -extrinsic factors influence blinatumomab response. We show that CD19 mutations are commonly detected in CD19− relapse during blinatumomab treatment. Identification of the CD19 ex2part splice variant represents a new biomarker predictive of blinatumomab therapy failure.

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