Conventional combinatorial anticancer therapy has shown promising outcomes; still, a significant interest in developing new methods to reinforce and possibly merge chemotherapy and immunotherapy persists.

Here, a new one-step method that immediately modifies immune cells into a targeted form of chemoimmunotherapy through spontaneous and rapid incorporation of hydrophobized antibody-drug conjugates (ADCs) on the surface of immune cells is presented.

Therapeutic objectives of this approach include targeted delivery of a potent chemotherapeutic agent to avoid adverse effects, enhancing the mobilization of infused immune cells toward tumor sites, and preserving the intense cytotoxic activities of immune cells against tumor cells.

The embedding of hydrophobized ADCs on the immune cell membrane using the strategy in this study provides noninvasive, nontoxic, and homogenous modifications that transiently arm immune cells with highly potent cytotoxic drugs targeted toward cancer cells.

The resulting surface-engineered immune cells with ADCs significantly suppress the tumor growth and drive the eradication of target cancer cells through combinatorial anticancer effects. This novel strategy allows convenient and timely preparation of advanced chemoimmunotherapy on a single immune cell to treat various types of cancer.

Chemoimmunotherapy

They demonstrated that our one?step method constitutes a new platform to produce the advanced form of chemoimmunotherapy that can achieve elevated levels of anticancer efficacy in many types of cancers including solid tumors and the product of the innovative mode of chemoimmunotherapy is promising.

Furthermore, this approach enables embedding any type of ADCs on the surface of any class of immune cells, including T cells, DCs, and macrophages, to transform them to combat a broad spectrum of cancers.

The applicability of surface?engineered immune cells is expected to be high because many new ADCs and new types of allogeneic immune cells currently undergoing discovery and development are viable candidates for our one?step method to generate advanced chemoimmunotherapy that potentially targets different types of cancers.

Fortunately, the conjugation of DMPE?PEGs to ADCs may circumvent the issue by masking the Fc region to increase the steric hindrance that lowers the binding affinity of Fc receptors on immune cells.

Other creative antibody engineering methods, such as using single-chain variable fragment (scFv) and altering Fc region to reduce Fc receptor binding affinity, can be employed as an alternative strategy for our surface engineering purpose.

The one?step method, a modular design allowing for the matching of allogeneic immune cells and ADCs based on needs, will be utilized to produce a wide range of targeted chemoimmunotherapy soon that adheres to the goal of creating “off?the?shelf” reagents.