One‐Step Method for Instant Generation of Advanced Allogeneic NK Cells

Abstract

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.

Research progress in leveraging biomaterials for enhancing NK cell immunotherapy

“…策略二：构建亲脂性抗体偶联药物，利用癌细胞特异性抗体提高NK细胞的识别效率与精度。通过疏水相互作用，可以即时高效地生产携带不同抗体偶联药物的NK细胞。Lee等 ［ 7 ］ 利用亲脂性抗体偶联药物赋予了NK细胞新功能。他们选用了模型抗体偶联药物曲妥珠单抗美坦辛（T-DM1），用DMPE对其进行疏水改造，构建了亲脂性抗体偶联药物DMPE-PEG-T-DM1。在共孵育过程中疏水端嵌入细胞膜，将抗体偶联药物锚定在NK细胞膜表面。该工程化策略不会损害NK细胞的活性，可利用PEG作为物理屏障阻止其内化，使其存在48 h以上。整个过程仅需15 min，实现了同种异体NK细胞疗法的高效生产。…”

New opportunities for immunomodulation of the tumour microenvironment using chemical tools

“…Won and Bull et al synthesised hydrophobized antibody–drug conjugates by attaching 1,2-dimyristoyl- sn-glycero -3-phosphoethanolamine-conjugated PEG to trastuzumab emtansine. 200 After mixing with NK cells, the conjugates were embedded in the cell membrane via lipid insertion, resulting in dual tumour targeting and killing functions. Some of these typical lipid groups are shown in Fig.…”

Immune Cycle‐Based Strategies for Cancer Immunotherapy

“…Some research has focused on the surface modification of NK cells to enhance the killing effects of NK cells on cancer cells. Won and co-workers [167] modified immune cells with antibody-drug conjugates (ADCs) to make them own specific targeting ability and chemotherapeutic effect in addition to the nonspecific cytotoxicity (Figure 11A). In their design, trastuzumab emtansine (T-DM1) as an ADC was connected with the conjugate formed by 1,2-dimyristoylsn-glycero-3-phosphoethanolamine (DMPE) and PEG.…”

“…Reproduced with permission. [167] Copyright 2018, Wiley-VCH GmbH. B) The construction of NK cells with aptamer TLS11A and PDL1-targeting aptamers.…”