Bridging the gap with multispecific immune cell engagers in cancer and infectious diseases.

By binding to multiple antigens simultaneously, multispecific antibodies are expected to substantially improve both the activity and long-term efficacy of antibody-based immunotherapy. Immune cell engagers, a subclass of antibody-based constructs, consist of engineered structures designed to bridge immune effector cells to their target, thereby redirecting the immune response toward the tumor cells or infected cells. The increasing number of recent clinical trials evaluating immune cell engagers reflects the important role of these molecules in new therapeutic approaches for cancer and infections. In this review, we discuss how different immune cell types (T and natural killer lymphocytes, as well as myeloid cells) can be bound by immune cell engagers in immunotherapy for cancer and infectious diseases. Furthermore, we explore the preclinical and clinical advancements of these constructs, and we discuss the challenges in translating the current knowledge from cancer to the virology field. Finally, we speculate on the promising future directions that immune cell engagers may take in cancer treatment and antiviral therapy.

NK Cell Therapeutics for Hematologic Malignancies: from Potential to Fruition.

PURPOSE OF REVIEW: The current review focuses on the preclinical development and clinical advances of natural killer (NK) cell therapeutics for hematologic malignancies and offers perspective on the unmet challenges that will direct future discovery in the field. RECENT FINDINGS: Approaches to improve or re-direct NK cell anti-tumor functions against hematologic malignancies have included transgenic expression of chimeric antigen receptors (CARs), administration of NK cell engagers including BiKEs and TriKEs that enhance antibody-dependent cellular cytotoxicity (ADCC) by co-engaging NK cell CD16 and antigens on tumors, incorporation of a non-cleavable CD16 that results in enhanced ADCC, use of induced memory-like NK cells alone or in combination with CARs, and blockade of NK immune checkpoints to enhance NK cytotoxicity. Recently reported and ongoing clinical trials support the feasibility and safety of these approaches. NK cell-based therapeutic strategies hold great promise as cost-effective, off-the-shelf cell therapies for patients with relapsed and refractory hematologic diseases.

Immune cell engagers in solid tumors: promises and challenges of the next generation immunotherapy.

In the landscape of cancer immunotherapy, immune cell engagers (ICEs) are rapidly emerging as a feasible and easy-to-deliver alternative to adoptive cell therapy for the antitumor redirection of immune effector cells. Even if in hematological malignancies this class of new therapeutics already hit the clinic, the development of ICEs in solid tumors still represents a challenge. Considering that ICEs are a rapidly expanding biotechnology in cancer therapy, we designed this review as a primer for clinicians, focusing on the major obstacles for the clinical implementation and the most translatable approaches proposed to overcome the limitations in solid tumors.