Combination of Immune Checkpoint Therapy with CAR-T Cell Therapy

Background

Immune checkpoint blockade (ICB) therapy has the capacity to induce long-lasting clinical responses through the reactivation of a fatigued immune response. Nevertheless, the efficacy of single ICB therapy is constrained by the absence of a tumor-responsive immune infiltrate. Chimeric antigen receptor T (CAR-T) cell therapy offers an effective solution to this limitation by furnishing the essential tumor-targeting immune infiltrate and a precision-oriented antitumor immune response. Augmentation of CAR-T cell therapy's effectiveness can be achieved by the incorporation of ICB agents, which can counteract the immune-inhibitory milieu that hampers the optimal efficacy of CAR-T cells.

Fig. 1 Strategies for rescuing CAR-T cell exhaustion through checkpoint blockade interventions.¹

CAR-T cell therapy has exhibited efficacy across a spectrum of malignancies, harnessing the immune system's prowess for cancer cell recognition and eradication. Nevertheless, when employed as standalone treatments, their therapeutic impact is less pronounced. Growing substantiation indicates that tumors can elude immune scrutiny by provoking inhibitory immune checkpoint receptors on T cells, encompassing CTLA-4 and PD-1. Such provocation gives rise to an immunosuppressive microenvironment that curtails the effectiveness of CAR-T cell therapy. Hence, the utilization of antibodies to obstruct these inhibitory immune checkpoints emerges as a promising strategy for augmenting the favorable outcomes of CAR-T treatment in solid tumors.

Case Study

The exploration of combinatory therapeutic approaches involving CAR‑T cell interventions and ICB has been extensively investigated in preclinical investigations, demonstrating promising outcomes. The synergy between CAR-T cell therapy and ICB has exhibited remarkable potential, culminating in sustained survival without manifesting any discernible pathological manifestations in vivo.


Fig. 2 Immune checkpoint inhibition with CAR-T cell combination therapy.² Checkpoint signaling operates as a regulatory mechanism for fine-tuning immune responses by attenuating excessive immune activation, thereby averting autoimmune reactions. Consequently, checkpoint blockade (CPB) has emerged as an increasingly captivating area of exploration in the realm of cancer immunotherapy. Tumor-derived checkpoint ligands orchestrate immune evasion by depleting the vigor of immune effector cells. Diverse investigations have reported remarkable outcomes stemming from the integration of CAR-T cell therapy with PD-1 blockade. Hence, the convergence of CAR-T cell and PD-1 CPB has engendered a burgeoning sphere of intrigue within the domain of CAR-T cell combination therapy.
	Fig. 3 The application of ICB and other therapies in hematologic malignancies.³ The integration of ICB involving PD-1/PDL-1 and CTLA-4 inhibitors with CAR-T therapy directed against CD19⁺ leukemia/lymphoma has irrevocably transformed the terrain of cancer treatment. The discovery of new immune checkpoints is poised to bridge the void in situations where existing therapeutics proved ineffective or in cases of disease recurrence.

Services at Creative Biolabs

Immune checkpoint molecules have been regarded as new targets for combating cancer, sparking significant enthusiasm in the realms of biological and preclinical investigations when integrated with CAR-T cell therapy.

Creative Biolabs extends an exhaustive suite of tailored, top-tier offerings encompassing immune checkpoint antibodies, proteins, peptides, assays, and small molecule drug development, with the aim of bolstering the pharmaceutical sector and the interconnected research communities in biomedical sciences worldwide. Our seasoned team with boasting years of expertise, stands ready to collaborate with you to ensure the products developed align precisely with your requisites:

References

Grosser, Rachel, et al. "Combination immunotherapy with CAR T cells and checkpoint blockade for the treatment of solid tumors." Cancer cell 36.5 (2019): 471-482.
Al-Haideri, Maysoon, et al. "CAR-T cell combination therapy: the next revolution in cancer treatment." Cancer Cell International 22.1 (2022): 1-26.
Wang, Hao, et al. "Immune checkpoint blockade and CAR-T cell therapy in hematologic malignancies." Journal of hematology & oncology 12.1 (2019): 1-20.

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