Combination of Immune Checkpoint Therapy with Other Types of Immunotherapy

Immunotherapy is a kind of cancer treatments using a patient’s own immune system to destroy cancerous cells. The immune checkpoint is of particular interest as one of the immunotherapies, with an activating agonistic antibody augments T cell differentiation and cytolytic function resulting in increased antitumor capacity against many types of tumors. As a first-class biological company in immunotherapy market, Creative Biolabs has established a series of therapeutic strategies to achieve the curative combination of immune checkpoints and many other immunotherapies. And our novel treatments can help clients to overcome the limitations, toxicities, and challenges of monotherapies and present impressive future research directions of combination therapies.

Overviews

When anti-checkpoint antibodies used as a single agent, they could induce potent immunologic responses in patients with metastatic diseases. However, each of these candidate agents only benefits a portion of patients, highlighting a critical need for more effective combinatorial strategies. Current clinical trials demonstrate that immune checkpoint therapies in the future will combine anti-cancer treatments that block signaling cascades, or identify tumor-associated antigens (TAA) that interrupt the tumor-induced immunosuppression, as well as vaccines that lead to antitumor immune responses, activated effector cells or chimeric antigen receptor-T (CAR-T) cells. All mentioned combinations also contain cytokines or anti-cytokine antibodies to burst the immune activity. The aim is to directly target tumor antigens or signaling pathways, and meanwhile interfere with the immune memory of the organism, to make patient’s body aware of tumor existence and simultaneously help it to evoke a strong antitumor response.

Combination Therapy Strategies at Creative Biolabs

Recent studies have emphasized the therapeutic efficacy of immunotherapy and provide a comprehensive review of immune checkpoint pathways. At Creative Biolabs, we have launched multiple rational combination therapies involved in cancer immunotherapy, in particular, the combination of immune checkpoint therapy with other types of therapies, which are listed as below.

Fig.1 Model of OX40 agonism in combination immunotherapy radiation and chemotherapy can induce the release of tumor-associated antigens by the tumor. (Linch, 2015)

• Agonistic antibody & CAR-T cell

Adoptive cellular therapy involving genetic modification of T cells with CAR transgene offers a promising platform to broaden the efficacy of this way for the treatment of cancer. Agonistic monoclonal antibodies that activate T-cell costimulatory receptors have advanced in their development, such as, α‐4‐1BB and α‐OX40 antibodies. Inclusion of 4-1BB and OX40 domains directly in the CAR construct as costimulatory signals have demonstrated a powerful ability to support CAR-T cell activation.

• Agonistic antibody & Inhibitor

PI3K inhibitor (phosphoinositide 3-kinase inhibitor) is a medical drug that functions by inhibiting phosphoinositide 3-kinase enzymes, which are part of the PI3K/AKT/mTOR pathway, controlling cell growth, metabolism and translation initiation. The use of OX40 agonist-based combination with PI3K inhibitor is emerging as a novel approach to improve the effectiveness of cancer treatment. OX40 (CD134) is a member of the tumor necrosis factor (TNF) receptor family and plays a key role in initiating signaling cascades for full activation of tumor-reactive T cells.

• Agonistic antibody & Oncolytic virus

The oncolytic herpes simplex virus (HSV) can be engineered with complementary safety mechanisms to reduce replication, neuropathic activity, and latency in normal cells while holding oncolytic ability in tumor cells. The combination of agonistic antibodies and oncolytic viruses can mediate potent antitumor efficacy in many syngeneic animal models, eliciting durable responses and protective immunity and enabling its clinical investigation on the treatment of metastatic cancers.

Advantages

• One-stop service package
• Many immunotherapeutic options on for the combination
• Long-lasting immune responses
• Applications extended to previously unanticipated tumor types

The anti-immune checkpoint antibodies allow the cure of patients lacking effective treatments, through the recovery of the patient’s own immune system against the tumor. The understanding of cellular and molecular mechanisms by which agonists synergize with multiple therapies create potential opportunities for clinical translation of combinatorial immunotherapeutic strategies. As a leading specialist in the antibody development field, Creative Biolabs provides customized solutions to construct varying combinatorial therapies among immune checkpoints and many other therapeutics. For more information, please feel free to contact us.

Reference

1. Linch, S.N.; et al. OX40 agonists and combination immunotherapy: putting the pedal to the metal. Front Oncol. 2015, 5: 34.

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