Magnetic Nanoclusters Armed with Responsive PD-1 Antibody Synergistically Improved Adoptive T-Cell Therapy for Solid Tumors

Abstract

Although adoptive T-cell therapy has been successful in hematological malignancy treatment, its application in solid tumors remains a great challenge. Here, using a pH-sensitive benzoic−imine bond and inverse electrondemand Diels−Alder cycloaddition, we prepared magnetic nanoclusters (NCs) armed with responsive PD-1 antibody (aP), which could then bind onto effector T cells due to their PD-1 expression. After adoptive transfer, the magnetization and superparamagnetism of NCs enabled us to magnetically recruit effector T cells and aP simultaneously to tumor sites with MRI guidance. Owing to the acidic intratumoral microenvironment, the benzoic−imine bond then hydrolyzed, leading to the release of aP. The therapeutic effects of adoptive T cells and free aP could thus be spatiotemporally coupled. As a result, we achieved inhibition of tumor growth with few side effects, demonstrating the great promise of such a chemical approach for safe and high-performance adoptive T-cell therapy against solid tumors.

Improving Tumor Retention of Effector Cells in Adoptive Cell Transfer Therapies by Magnetic Targeting

“…The use of MNPs together with localized EMFs could improve the targeting of these genetically modified lymphoid cells and enhance antitumor immune response. An example of this type of strategy has been recently published by Nie et al In this work magnetic nanoclusters loaded with PD-1 antibody and bound to effector T cells were used as a platform to magnetically recruit effector T cells and PD-1 antibody simultaneously to the tumor with MRI guidance [206] resulting in inhibition of tumor growth in a murine model. It would also be important for the application of this nanotechnology to develop synthesis methods that could be easily scaled-up and standardized as well as performed in a hospital clean room to allow for their implementation in clinical settings.…”

“…The use of MNPs together with localized EMFs could improve the targeting of these genetically modified lymphoid cells and enhance antitumor immune response. An example of this type of strategy has been recently published by Nie et al In this work magnetic nanoclusters loaded with PD-1 antibody and bound to effector T cells were used as a platform to magnetically recruit effector T cells and PD-1 antibody simultaneously to the tumor with MRI guidance [ 206 ] resulting in inhibition of tumor growth in a murine model.…”

Organic Semiconducting Pro‐nanostimulants for Near‐Infrared Photoactivatable Cancer Immunotherapy

“…For example, an imidazoquinoline pro‐immunostimulant was synthesized to only become active in the presence of α‐mannosidase enzyme overexpressed in many cancer cells, and a reduction‐activatable protein nanoparticle was designed to selectively release cytokines in response to the elevated level of biothiols on activated T‐cell surfaces to enable a localized immunotherapeutic window . In addition, magnetic nanoclusters were developed to release programmed cell death protein 1 (PD‐1) antibody at acidic pH to improve adoptive T‐cell cancer therapy and minimize its side effects . However, these immunostimulatory agents rely on the endogenous biomarkers associated with tumor microenvironment, which also exist in other normal tissues/cells .…”

Codelivery of Anti‐PD‐1 Antibody and Paclitaxel with Matrix Metalloproteinase and pH Dual‐Sensitive Micelles for Enhanced Tumor Chemoimmunotherapy

“…It is well‐known that polymeric nanocarriers may improve the therapeutic effects and lessening the side effects of chemotherapeutic drugs . Moreover, polymeric nanocarriers may be readily engineered to encapsulate different types of drugs and achieve a programmed site‐specific drug delivery, which make them a proper candidate to mediate chemoimmunotherapy . Nevertheless, it is a challenging task to construct polymeric nanocarriers which respond to the stimuli of tumor microenvironment to release anti‐PD‐1/PD‐L1 antibodies and chemotherapeutic agents in a spatio‐temporally controlled manner, so that the two drugs can act on their own targets for a synergistic therapy.…”