Combination Among Different Immune Checkpoint Therapies

Immune checkpoints consist of stimulatory and inhibitory pathways that benefit to maintain self-tolerance and help immune responses. In cancers, checkpoint molecules are usually activated to inhibit the nascent antitumor immune activities. Immunotherapies targeting checkpoints act by stimulating or blocking these pathways and improve the body's immunological reactions against tumors. As a famous supplier in the biotechnological field, Creative Biolabs is committed to studying the agonists of stimulatory checkpoint pathways, including OX40, 4-1BB, ICOS, GITR, CD40, and provides a range of optimal combination therapies for effective treatment, in particular, the combination among different checkpoint-mediated agonistic antibodies.

Overviews

Immune checkpoint blockade with antagonistic monoclonal antibodies targeting CTLA-4, PD-1, and PD-L1 (B7 immunoglobulin superfamily) generate long-term antitumor immune responses across many cancer types. Nevertheless, numerous patients are basically resistant to checkpoint blockade-based monotherapy and most of them eventually relapse. Hence, novel immunostimulatory targets are required to overcome primary and secondary defense to immunotherapy, such as OX40 (CD134). This is a co-stimulatory molecule that has been expressed by activated immune cells. Furthermore, anti-OX40 agonistic antibodies are supposed to combine with several co-inhibitory molecules, which have been tested in the early phase of cancer occurrence, like melanoma. And accumulative preclinical evidence supports their clinical development on combinational drugs.

Combination Therapy Strategies at Creative Biolabs

In general, unique combinations consist of mixtures of checkpoint antibodies against either different epitopes of the same target or different molecules on the same tumor cell; bispecific or multispecific antibodies able of simultaneously binding immune cells, tumor cells, or extracellular molecules. Through complementary mechanisms of action, these combinations contribute to eluding the current limitation of a single antibody only recognizing one particular epitope. Meanwhile, these combinations may allow the simultaneous attack of cancer cells by exploiting the help of own immune cells and exerting wider therapeutic effects, based on a fast, specific, and robust immune responses.

Agonistic antibodies targeting checkpoint proteins have proven their high value in antitumor therapy over the last years. The strategies to combine multiple checkpoints are recently being considered as the first-choice to treat some of the most common metastatic cancers, just like colorectal cancers or breast cancers. Besides B7 receptor superfamily, Creative Biolabs provides a variety of antibodies against different immune checkpoints, for example, the members of tumor necrosis factor receptor superfamily, which have a potential to become the next generation immunomodulators. On the other hand, we also focus on a large number of immune checkpoint therapy combinations (e.g. anti-CD20 & anti-CCR4; anti-CD137 & anti-PD-1; anti-PD1 & anti-OX40) under tests and would like to cooperate with global scientists to face these challenging projects.

Fig.1 Structure of OX40 compared to CTLA4 and PD-1. (Aspeslagh, 2016)

Features

Abundant immune checkpoints can be chosen
Expertise in the rational combination of anti-checkpoints antibodies
Rich experience in agonistic antibody development and clinal therapies
Potent platforms & advanced technologies

The impressive success of agonistic antibodies inhibiting immune checkpoints has expanded the usage of therapeutic antibodies to previously unanticipated tumor types. As a well-known expert in the antibody market, Creative Biolabs reviews immune checkpoint pathways involved in cancer immunotherapy and evaluates combination therapeutic interventions under investigation in each phase of clinical trials. Also, we’re able to assist customers to design next-generation agonistic antibodies with greater efficacy. For more information, please feel free to contact us.

Reference

Aspeslagh, S.; et al. Rationale for anti-OX40 cancer immunotherapy. Eur J Cancer. 2016, 52: 50-66.

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