Nanotechnology and immunoengineering: How nanotechnology can boost CAR-T therapy

Chimeric antigen receptor (CAR) therapy has achieved remarkable clinical efficacy against hematological cancers and has been approved by FDA for treatment of B-cell tumors. However, the complex manufacturing process and limited success in solid tumors hamper its widespread applications, thus prompting the development of new strategies for overcoming the abovementioned hurdles. In the last decade, nanotechnology has provided sustainable strategies for improving cancer immunotherapy through vaccine development and delivery of immunomodulatory drugs. Nanotechnology can boost CAR-T therapy and may overcome the existing challenges by emerging as a carrier for CAR-T therapy or in combination with CAR-T, it may inhibit solid tumors more effectively than conventional approaches. The revealing of cellular mechanisms, barriers and potential strategies that could be used to manipulate and/or modify cells would enable unprecedented advances in nanotechnology for biologics delivery. This review outlines the journey and barriers of nanoparticles (NPs) across the cell. Subsequently, the approaches to tackle the barriers and strategies to modulate NPs as a carrier for CAR-T therapy are discussed. Finally, the role of NPs in CAR-T therapy and the potential challenges are summarized. This review aims to provide the readers with a detailed overview of NP-based CAR-T therapy research and distil this information into an accessible form conducive to design desired CAR-T therapy using NP approach. STATEMENT OF SIGNIFICANCE: Chimeric antigen receptor (CAR) T-cell therapy is the most vibrant field in immuno-oncology today, with enormous benefits to patients with B-cell malignancies. However, a rapid and straightforward procedure for CAR-T generation is an exigent need to broaden its therapeutic avenue. Nanotechnology has emerged as a novel alternative approach for CAR-T generation. To the best of our knowledge, this is the first in-depth review that briefly highlights the various aspects of nanotechnology in CAR-T therapy, including the strategies to brand NPs as an effective carrier for CAR cargo, its potential advantages, challenges, and future roadmap. It provides readers with a detailed overview of NP-based CAR-T therapy research, and researchers would be able to distill this information into an accessible form conducive to design the desired CAR therapy using the nanotechnology approach.