A conceptual breakthrough in cancer treatment! These are studying three specific antibodies, you know?

Transfer from . On August 17th, Ze-Yuan Pharmaceuticals introduced a new three-specific antibody drug for more than $5 million, raising concerns about three-specific antibodies.
we know that monosexual monoclonal antibodies were the first to be widely used in cancer immunotherapy, such as anti-PD-1/PD-L1 antibodies.
, dual-specific antibodies that can target both targets at the same time began to receive attention, such as Bite therapy Blincyto, which targets CD19 and CD3 receptors.
, what's unique about the three specific antibodies that have recently begun to appear in people's sights? Which companies are currently involved in this area? This article will be an antho-section on drugs and companies to share with you.
1, Sanofi usually activates one end of the T-cell-specific T-cell bridging protein to the target on the tumor surface and the other end to the CD3 subject on the surface of the T-cell.
these molecules can activate T cells, they also induce cell death caused by T-cell activation without simultaneously activating the costulation signaling path.
this limits the anti-cancer activity of T cells to some extent.
in addition to binding to cd3 binds, Sanofi develops three-specific T-cell bridging proteins that bind to CD3 binds to the co-stimulation subject CD28, while activating the CD28 signaling path path can promote the survival of activated T-cells and produce "T-cell memory".
SAR442257, developed based on this technology platform, is a three-specific antibody targeting CD38.
in-body tests showed 1000 to 10,000 times higher myeloma cell killer activity than CD38 monoclonal antibodies.
, this trisexual antibody is currently in clinical trials to treat patients with recurring/refractic multiple myeloma (MM) and non-classical Hodgkin's lymphoma (NHL).
2, Numab Therapeutics/Keystone Pharmaceuticals Numab is committed to developing treatments for cancer and autoimmune diseases.
ND021 is a unit-priced three-specific antibody chip molecule (scMATCH3™) developed by Numab based on its unique scap™technology and MATCH™ platform, which can be combined with PD-L1, 4-1BB and HSA.
multisexual MATCH molecules can be composed of multiple all-humanized sFv fragments.
these molecules are highly stable and easy to create new mechanisms of action (such as tumor-targeted T-cell activation) through Numab's "plug-and-play" engineering techniques, resulting in the development of new multi-functional drug molecules.
According to the Numab press release, ND021 is only combined with the unique antigen supersem of 4-1BB in combination with PD-L1 on the surface of tumor cells to activate cancer-fighting T-cells, thus avoiding the hepatotoxicity observed in human trials with the traditional 4-1BB agitant monoantitor.
in preclinical models, ND021 showed good tolerance and was able to induce precise anti-tumor response.
its unique molecular structure and binding properties, which can translate into significant clinical benefits in a wide range of cancer patients.
note that in May 2019, Keystone Pharmaceuticals entered into a regional exclusive licensing agreement with Numab for the drug ND021.
Under the agreement, Cornerstone Pharmaceuticals will fund the development of ND021 until the completion of the initial Phase I Clinical Trials, while Keystone Pharmaceuticals will have exclusive rights to develop and commercialize ND021 in Greater China (including Chinese mainland, Hong Kong, Macau and Taiwan), South Korea and Singapore.
Numab retains all rights to the drug candidate in the rest of the world.
3, Gensun Biopharma/Zee Tse-pharma announced on August 17 that it had signed an Exclusive License Agreement with its controlling subsidiary Gensun Biopharma to develop and obtain exclusive patent licenses for ZGGS001, a new antibody drug, in Greater China, including Chinese mainland, Hong Kong, Macau and Taiwan.
the agreement, Zee-Pharma will pay a fixed payment of $5 million to GENSUN.
according to the announcement, ZGGS001 is a novel three-specific antibody molecule, mainly inhibit tumor immunity and multiple tumor angiogenesic pathways, regulate tumor micro-environment.
ZGGS001 can bind and inhibit three different targets at the same time, and has no interaction and binding interference with each other, and shows good tumor growth inhibition in the body.
addition, ZGGS001 has good expression, stability and medicinal quality.
announcement, as a new protein drug, GENSUN has carried out some research on ZGGS001 in the areas of mechanism of action, pharmacology and preclinical pharmacoetics, which can provide a technical basis for the follow-up development of the project.
the product is currently in preclinical development.
4, Numab Therapeutics/Sansheng Guojian in December 2019, Sansheng Pharmaceuticals subsidiary Sansheng Guojian and Numab Corporation reached a partnership to develop and commercialize a range of new multisexual antibodies for cancer treatment based on Numab's technology platform.
Under the agreement, Sansheng has the right to select up to five antibody molecules in three multisexual antibody projects on the Numab research and development platform and to have exclusive licensing rights for the development and commercialization of selected antibody molecules in Greater China, including Chinese mainland, Hong Kong, Macau and Taiwan.
5, Teneobio Teneobio is dedicated to using its TeneoSeek antibody discovery engine to quickly identify a large number of unique molecules that can be combined with specific therapeutic targets for the treatment of cancer, autoimmune diseases and infectious diseases.
teneobio has previously signed a partnership agreement between GlaxoSmithKline (GSK) and Janssen Pharmaceuticals Inc., a unit of Johnson and Johnson, to develop the next generation of oncology immunotherapy, multisexual antibodies, according to the company's website.
6, in addition to the above products and involved in the company, there are some early research has been published in internationally renowned journals.
: In 2017, a study published in the journal Science showed that scientists had developed a three-specific antibody in the lab that protects monkeys from two strains of the human monkey-embedded immunodeficiency virus (SHIV).
it is reported that this three-specific antibody will be widely neutral with the HIV antibody VRC01, PGDM1400 and 10E8v4 unique structure combined, three HIV binding fragments derived from three natural antibodies, each natural antibody is powerful to neutral many HIV strains.
researchers say the three-specific antibody's ability to bind to three different targets at the same time could provide a strong basis for developing treatments for HIV infections, other infectious diseases, autoimmune diseases and cancer.
looking ahead, as the paper in Science says, the use of trisexual antibodies to target cancer is a very important conceptual breakthrough, and these studies have yielded good results in preclinical studies.
Because trisexual antibodies are a flexible vector that can specifically transmit immunomodulation signal combinations in tumor micro-environments, this may be safer and more effective than multiple specific immunomodulation monoantibodies.
, this combination strategy is expected to improve the accuracy and efficacy of current immunotherapy and further expand the scope of immunotherapy.
References: Garfall and June. (2019). Trispecific antibodies offer a third way forward for anticancer immunotherapy. Nature, doi: 10.1038/d41586-019-03495-3. Retrieved Aug 17, 2020, from Sansheng Guojian teamed up with Numab to develop a new type of tumor immune polysexual antibody. Retrieved Dec 12, 2019, from Numab Therapeutics Close Series B Financing at CHF 22M to Advanced Portfolio of Novel Multi-specific Antibodies in Immuno-Oncology, Retrieved March 09, 2020, from R&D Investor Event. Retrieved June 23, 2020, from Lan Wu et al. Trispecific antibodies enhance the therapeutic efficacy of tumor-directed T cells through t cell receptor co-stimulation. Nature Cancer (2019). Ling Xu, Amarendra Pegu, Ercole Rao et al. Trispecific broadly neutralizing HIVbodies antibodies mediate potent SHIV protection in macaques. Science. Follow Medicinal Mingkangd on WeChat Public No.