teplizumab

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Ligands
teplizumab

GtoPdb Ligand ID: 12252

Synonyms: humanized OKT3 | MGA031 | PRV-031 | teplizumab-mzwv | Tzield®

teplizumab is an approved drug (FDA (2022))

Comment: Teplizumab is a humanized anti-CD3e monoclonal antibody that was originally developed as an immunomodulatory agent. Structurally it is a modified version of the mouse antibody muromonab-CD3 (mOKT3) that has been used to reverse steroid-resistant renal allograft rejection. Alterations in the OKT3 CH2 domain disrupt Fcγ receptor binding, and blocks antibody-mediated effector cells functions and cytokine release [5,7]. It was advanced to extended clinical evaluations for potential to protect pancreatic β-cells in newly diagnosed type 1 diabetes (T1D) patients [4,6], following evidence that it impaired expansion of alloreactive anti-β cell T cells [5], and that a single short course of teplizumab treatment could induce a long-lasting improvement in patients' C-peptide responses and clinical parameters (including preservation of insulin production) in the early stages of T1D [2-3].

References
1. Herold KC, Bundy BN, Long SA, Bluestone JA, DiMeglio LA, Dufort MJ, Gitelman SE, Gottlieb PA, Krischer JP, Linsley PS et al.. (2019) An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. N Engl J Med, 381 (7): 603-613. [PMID:31180194]
2. Herold KC, Gitelman SE, Ehlers MR, Gottlieb PA, Greenbaum CJ, Hagopian W, Boyle KD, Keyes-Elstein L, Aggarwal S, Phippard D et al.. (2013) Teplizumab (anti-CD3 mAb) treatment preserves C-peptide responses in patients with new-onset type 1 diabetes in a randomized controlled trial: metabolic and immunologic features at baseline identify a subgroup of responders. Diabetes, 62 (11): 3766-74. [PMID:23835333]
3. Herold KC, Gitelman SE, Masharani U, Hagopian W, Bisikirska B, Donaldson D, Rother K, Diamond B, Harlan DM, Bluestone JA. (2005) A single course of anti-CD3 monoclonal antibody hOKT3gamma1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes, 54 (6): 1763-9. [PMID:15919798]
4. Masharani UB, Becker J. (2010) Teplizumab therapy for type 1 diabetes. Expert Opin Biol Ther, 10 (3): 459-65. [PMID:20095914]
5. Popma SH, Griswold DE, Li L. (2005) Anti-CD3 antibodies OKT3 and hOKT3gamma1(Ala-Ala) induce proliferation of T cells but impair expansion of alloreactive T cells; aspecifc T cell proliferation induced by anti-CD3 antibodies correlates with impaired expansion of alloreactive T cells. Int Immunopharmacol, 5 (1): 155-62. [PMID:15589476]
6. Skelley JW, Elmore LK, Kyle JA. (2012) Teplizumab for treatment of type 1 diabetes mellitus. Ann Pharmacother, 46 (10): 1405-12. [PMID:22968521]
7. Xu D, Alegre ML, Varga SS, Rothermel AL, Collins AM, Pulito VL, Hanna LS, Dolan KP, Parren PW, Bluestone JA et al.. (2000) In vitro characterization of five humanized OKT3 effector function variant antibodies. Cell Immunol, 200 (1): 16-26. [PMID:10716879]
8. (2020) An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. N Engl J Med, 382 (6): 586. [PMID:32023396]

References

1. Herold KC, Bundy BN, Long SA, Bluestone JA, DiMeglio LA, Dufort MJ, Gitelman SE, Gottlieb PA, Krischer JP, Linsley PS et al.. (2019)
An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes.
N Engl J Med, 381 (7): 603-613. [PMID:31180194]

2. Herold KC, Gitelman SE, Ehlers MR, Gottlieb PA, Greenbaum CJ, Hagopian W, Boyle KD, Keyes-Elstein L, Aggarwal S, Phippard D et al.. (2013)
Teplizumab (anti-CD3 mAb) treatment preserves C-peptide responses in patients with new-onset type 1 diabetes in a randomized controlled trial: metabolic and immunologic features at baseline identify a subgroup of responders.
Diabetes, 62 (11): 3766-74. [PMID:23835333]

3. Herold KC, Gitelman SE, Masharani U, Hagopian W, Bisikirska B, Donaldson D, Rother K, Diamond B, Harlan DM, Bluestone JA. (2005)
A single course of anti-CD3 monoclonal antibody hOKT3gamma1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes.
Diabetes, 54 (6): 1763-9. [PMID:15919798]

4. Masharani UB, Becker J. (2010)
Teplizumab therapy for type 1 diabetes.
Expert Opin Biol Ther, 10 (3): 459-65. [PMID:20095914]

5. Popma SH, Griswold DE, Li L. (2005)
Anti-CD3 antibodies OKT3 and hOKT3gamma1(Ala-Ala) induce proliferation of T cells but impair expansion of alloreactive T cells; aspecifc T cell proliferation induced by anti-CD3 antibodies correlates with impaired expansion of alloreactive T cells.
Int Immunopharmacol, 5 (1): 155-62. [PMID:15589476]

6. Skelley JW, Elmore LK, Kyle JA. (2012)
Teplizumab for treatment of type 1 diabetes mellitus.
Ann Pharmacother, 46 (10): 1405-12. [PMID:22968521]

7. Xu D, Alegre ML, Varga SS, Rothermel AL, Collins AM, Pulito VL, Hanna LS, Dolan KP, Parren PW, Bluestone JA et al.. (2000)
In vitro characterization of five humanized OKT3 effector function variant antibodies.
Cell Immunol, 200 (1): 16-26. [PMID:10716879]

8. (2020)
An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes.
N Engl J Med, 382 (6): 586. [PMID:32023396]