Next-IO™ Anti-4-1BB Monoclonal Antibody Program

About This Program

This program aims to develop anti-4-1BB monoclonal antibody that has therapeutic use in immuno-oncology.

Agonistic monoclonal antibody targeting 4-1BB has been developed to utilize 4-1BB signaling for cancer immunotherapy. Preclinical results of various tumor models indicate that targeting 4-1BB with agonist antibodies can lead to tumor clearance and persistent anti-tumor immunity. For this reason, multifunctional modulator 4-1BB has become a promising target for exploration in cancer immunotherapy.

4-1BB

4-1BB (CD137, Tumor Necrosis Factor Receptor Superfamily 9) is an inducible costimulatory receptor, which is expressed in activated T and natural killer (NK) cells. The 4-1BB ligation on T cells triggers a signaling cascade that leads to upregulation of anti-apoptotic molecules, cytokine secretion and enhanced effector function. In dysfunctional T cells with reduced cytotoxic capacity, the 4-1BB linkage shows an effective ability to restore effector function.

As shown in Fig1:

• (A) Agonistic anti-4-1BB mAb therapy induces T-cell proliferation and cytokine secretion.
• (B) On NK cells, stimulation of 4-1BB enhances ADCC.
• (C) Agonistic anti-4-1BB mAbs can also stimulate DCs and macrophages to emit anti-tumor immune responses. 4-1BB is expressed in tumor-associated vascular endothelium.
• (D) Bispecific antibodies are capable of targeting both 4- 1BB and tumor antigens, such as HER2, locking immune effectors and targeting closely located cells to facilitate tumor cell lysis.

Anti-4-1BB Antibody Research Among Cancer Studies

Anti-4-1BB antibody is often used in combination with other immunology agents in clinical researches to achieve anti-tumor effects. Below are some published data about 4-1BB as a potential target for cancer immunotherapy.

• The efficacy of vaccines with and without 4-1BB mAb to inhibit the development of lymphoma.

• Anti–4-1BB/anti–PD-1 combination treatment in melanoma.

• Fibrosarcoma (MCA 205) and glioma (GL261) were treated with either 4-1BB mAbs 3E1 or 1D8.

Indication

Based on the published data, we learn that the 4-1BB is highly expressed in different types of tumors, such as B-cell Lymphoma, melanoma, glioma, and sarcomas. Therefore, we hope to develop multiple mAb programs that are applicable to different indications (not limited to one specific type of tumor), of which 4-1BB is highly expressed.

Clinical Trials under Progress

Currently, multiple 4-1BB-targeted bispecific antibodies have been used in preclinical or early clinical researches. Multiple efforts have also been put into the filed to develop therapeutic strategies that maximize 4-1BB agonism while minimizing systemic exposure and 4-1BB-induced toxicity. However, many mechanistic problems still remain unresolved yet.

Despite this, 4-1BB is still a very compelling target for cancer immunotherapy. In an effort to optimize 4-1BB–mediated immune activation, the next-generation 4-1BB targeting strategy use a combination therapy with other immunomodulatory agents to advance the trial. We believe that this particular approach could achieve greater success in the treatment of various cancers.

Program Plan

With our extensive experience in providing CRO services, we are confident of providing streamlined end-to-end program. We are committed to developing a complete program, from antibody discovery, engineering, optimization, to pre-clinical studies, according to the needs of our partners,. Periodic progress report will be delivered to our clients for effective, smooth and timely communication.

Fig.1 The timeline of Next-IO™ programs.

Collaboration

Creative Biolabs is looking for potential partners (including but not limited to major pharma or biotech firms) to develop anti-4-1BB monoclonal antibody program together. Our scientists are dedicated to bringing years of valuable experience to our partner and enabling a meaningful partnership. By using this strategic collaboration, we wish to help both sides to proceed with IND and many stages of clinical trials.

If you are interested in our program, please feel free to contact us to learn more about the cooperation. Looking forward to working with you in the near future.