Enumeral公司抗PD-1抗体发现结合位点：
1.不与已知PD-1抗体竞争结合
2.也不与PD-L1竞争
3.体外有肿瘤免疫治疗生物学活性
4.活性与T细胞的CD25表达有量效关系（目前类似靶点抗体无）
可能开发单药更优，也可与现有的PD-1以及PD-L1单抗联合使用，类似HER2靶点上的曲妥珠单抗与帕妥珠单抗。
来源
Enumeral Announces Identification of Anti-PD-1 Antibodies with Potential for Differentiated Mechanism of Action
Published on Thursday, 24 September 2015
Provides Update on Additional Antibody Programs Against TIM-3 and LAG-3
CAMBRIDGE, MA, USA I September 24, 2015 I Enumeral Biomedical Holdings, Inc. (OTCQB:ENUM), a biotechnology company focused on discovering and developing novel antibody immunotherapies that help the immune system fight cancer and other diseases, today announced important progress in its anti-PD-1 antibody program. Enumeral also provided an update on the progress of additional programs in the Company’s R&D pipeline, including its TIM-3 and LAG-3 antibody programs.
Earlier this year, Enumeral announced the identification of antibodies that appear to bind to the PD-1 inhibitory checkpoint protein in a manner different from that of currently marketed anti-PD-1 antibodies, while retaining activity in cell-based assays. Today Enumeral reported that these novel antibodies do not appear to compete with currently marketed antibodies for binding to PD-1, nor do they appear to compete with PD-L1, providing further evidence of a differentiated mechanism of action. Enumeral presented these and related findings during the recent CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference and the Biopharm America Conference. The Company’s poster and presentation from those respective conferences are available on Enumeral’s website.
“Since these antibodies do not compete with PD-L1, yet still display activity in relieving the immunosuppressive effects of PD-L1, they may prove useful in treating patients who have failed prior PD-1 therapy. Further, this potentially distinct class might be synergistic when combined with other PD-1 pathway-directed therapies, including anti-PD-L1 therapy, which we are planning to test in preclinical models,” commented Arthur H. Tinkelenberg, Ph.D., President and Chief Executive Officer of Enumeral.
Enumeral has isolated and sequenced more than 300 anti-PD-1 antibodies from primary B cells. The Company has humanized two lead antibodies and tested them in cell-based assays. As reported at the recent immunotherapy meeting, Enumeral’s novel family of antibodies exhibits a higher level of T cell activation in mixed lymphocyte reaction (MLR) and other assays than associated with currently-marketed antibodies, including:
Enumeral’s lead antibodies demonstrated increased interferon gamma production as shown by MLR assay, which is designed to assess T cell effector function using primary human immune cells.
These antibodies also demonstrated dose-dependent increases in T cell CD25 expression.
“This activity may be partially responsible for the elevated production of interferon gamma, perhaps through an autocrine IL-2 signaling mechanism, in contrast to other types of antibodies, which do not appear to have an effect on CD25 expression. Based on the evidence in the literature, we have had a strong rationale to pursue an alternative approach to PD-1 antagonism with the goal of improving initial response rates in patients treated with anti-PD-1 therapy,” noted Cokey Nguyen, Ph.D., Enumeral’s Vice President of Research and Development.
“Approved antagonists do not appear to exhibit dose-dependent pharmacologic effects, and their reported affinities for the PD-1 protein vary widely, which suggests to us that the mechanism of action of these agents is not fully understood. Therefore, there might be an opportunity to identify a potential ‘best in class’ agent. Based on our industry-leading discovery platform, we set out to find mechanistically distinct antibodies that exhibited enhanced function in immunomodulation assays,” Dr. Nguyen continued.
Enumeral is further investigating the mechanism of action of these differentiated antibodies, and has initiated testing in immuno-humanized mouse models of cancer, which enable testing of PD-1 modulatory therapies. The Company expects data from these studies to be available in December 2015.
“We set out to use our platform technology to identify novel potential ‘best-in-class’ antibodies that would improve immunotherapy response rates in the initial treatment of cancer. We are excited by the potential for these novel antibodies to broaden the effectiveness of checkpoint therapy by providing PD-1 antibodies with an alternative mechanism of action,” added Dr. Tinkelenberg.
In Enumeral’s TIM-3 program, the Company has isolated 124 TIM-3 binding antibodies to date. Enumeral’s bioinformatics analysis indicates desirable diversity, with the antibodies falling into 42 distinct clades that bind to TIM-3. Enumeral plans to apply its unique approach to cellular immune response profiling to further understand the utility of these different antibodies for modulation of different tumor infiltrating lymphocytes.
Enumeral believes antibodies that block TIM-3 may potentiate anti-cancer immune responses, either as a monotherapy or in combination with other therapies, including other immune checkpoint-targeted drugs. The Company currently anticipates nominating lead clones in the fourth quarter of 2015, and beginning the humanization process by the end of this year.
In Enumeral’s LAG-3 program, the Company has isolated 102 LAG-3 binding antibodies that fall into 40 distinct clades that bind to LAG-3. The Company is currently in the process of selecting antibody clones for further characterization.
About Enumeral
Enumeral is a biopharmaceutical company discovering and developing novel antibody immunotherapies that help the immune system fight cancer and other diseases. The Company is building a pipeline focused on next-generation checkpoint modulators, with initial targets including PD-1, TIM-3, LAG-3, OX40, and VISTA. In developing these agents, Enumeral’s researchers apply a proprietary immune profiling technology platform that measures functioning of the human immune system at the level of individual cells, providing key insights for candidate selection and validation. For more information on Enumeral, please visit www.enumeral.com.
SOURCE: Enumeral