As a thriving CRO company, Creative Biolabs has the initiative to acquire, develop and commercialize Next-IO™ programs with a goal to treat cancers. Our anti-BTLA monoclonal antibody program aims to develop therapeutic monoclonal antibodies that could recognize and potentially, against B and T lymphocyte attenuator (BTLA).

Background

Immune checkpoints are critical in maintaining immune homeostasis. In cancer management, immune checkpoints play a vital role in immune suppression to promote tumorigenesis. Recently, cancer immunotherapy achieved major clinical success, with immune checkpoint inhibitors being the center in the stage. For example, antibodies targeting immune checkpoints - PD1 and CTLA4 have shown promising results in various cancers. However, because of the individual difference, not all cancer patients benefit from these therapies. There are substantial interests in exploring different immune checkpoint molecules that may act as therapeutic targets. This program focuses on the cancer immunotherapies targeting BTLA, which is an inhibitory immune checkpoint that plays an important role in immune suppression.

Mechanism of Action

B and T lymphocyte attenuator (BTLA) is a protein belongs to the CD28 Ig domain superfamily and expressed by a majority of lymphocytes. The cytoplasmic domain of BTLA consists of three motifs; an immunoreceptor tyrosine-based inhibition motif (ITIM), an immunoreceptor tyrosine-based switch motif (ITSM), and a growth factor receptor-bound protein 2 motif (Grb2). The ligand of BTLA can interact with herpesvirus entry mediator (HVEM), a tumor necrosis factor receptor (TNF) superfamily member. The interaction between BTLA and HVEM is unique. It releases bidirectional signaling that needs to be regulated appropriately to keep the immune balance. Inhibitory signals will be released once HVEM engagement of BTLA via SH2 domain (see Fig.1). As one of the novel co-inhibitory receptors, BTLA shows structural and functional similarities with PD-1 and CTLA-4.

Our Anti-BTLA mAb Program

The anti-BTLA monoclonal antibody will be designed to binds to BTLA, specifically. The aim is to achieve a reversal of immune suppression and boost anti-tumor responses in patients with cancers. Our program consists of early antibody discovery and engineering phase, antibody optimization and production phase, a series of in vitro and in vivo validation studies and even IND enabling. Studies have shown that anti-BTLA works better with other checkpoint inhibitors (see Fig.2). For combination therapies, please reach out to our scientists for additional assistance.

Published Data

• BTLA is downregulated by progressive CD8⁺ T cell differentiation, except in tumor antigen-specific CD8⁺ T cells.
• Anti-BTLA antibodies induce cytotoxic lymphocyte marker expression.

Fig.1 Anti-BTLA antibodies induce cytotoxic lymphocyte marker expression.¹

• Anti-BTLA antibodies reduce tumor growth.

Fig.2 Anti-BTLA antibodies reduce tumor growth.¹

Based on these data, we can learn anti-BTLA exhibits promising therapeutic benefits in cancer treatments. Moreover, anti-BTLA shows better anti-tumor outcomes in combination with blockade of other immune checkpoints, such as PD-1 inhibitor.

Ongoing Clinical Trials

So far, monoclonal antibodies developed against programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have all shown some level of anti-tumor efficacy, and several antibodies have already approved by officials to use in practice. BTLA, as a key immune checkpoint, is currently being evaluated in many studies and clinical trials. Till today, not one drug anti-BTLA is approved. We believe our program of discovering and researching on anti-TIGIT is at the cutting edge of the field and have certain marking and sale potential.

Program Planning and Management

With extensive experience in the discovery and development of therapeutic antibodies, Creative Biolabs is dedicated to providing Next-IO™ programs to our clients efficiently. We commit to delivering the completed program to our partners within about 1.5 years. The accurate timeline will be determined on a case-by-case basis. Here is a draft timeline for a glance.

Fig.3 The timeline of Next-IOᵀᴹ programs.

Collaboration

Creative Biolabs is excited to offer years of valuable CRO experience to our partners and achieve more strategic collaborations together. We are dedicated to maximizing the success of our programs in a timely manner. As a leading CRO, we believe our collaboration will unleash the creative spirit and achieve greater success in the field of immuno-oncology.

If you are interested in our programs, please feel free to contact us for more details.

Reference

• Sekar, Divya, et al. "Downregulation of BTLA on NKT cells promotes tumor immune control in a mouse model of mammary carcinoma." International journal of molecular sciences 19.3 (2018): 752.

For Research Use Only | Not For Clinical Use