Dual-functional super bispecific nano-antibodies derived from monoclonal antibodies potentiate the antitumor effect of innate immune cells

Chen, Kai-Ge; Liu, An; Jiang, Cheng‐Tao; Zhao, Dong-Kun; Ye, Qian-Ni; Liao, Yu-Qi; Xu, Cong; Shen, Song; Wang, Jun

doi:10.1016/j.nantod.2021.101209

Cited by 11 publications

(6 citation statements)

References 41 publications

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“…NK cell function is governed by a complex set of activating and inhibitory receptors that do not require tumor-specific antigens or antigen-presenting cell activation [ 11 ]. The expression of various ligands on cancer cells reportedly modulates the function of NK cells [ 12 , 13 ]. Therefore, screening and identification of cancer types that are sensitive to NK cell killing activity would improve the outcomes of strategic decision making for NK cell therapies.…”

Section: Introductionmentioning

confidence: 99%

Anti-Tumor Activity of Expanded PBMC-Derived NK Cells by Feeder-Free Protocol in Ovarian Cancer

Chen

et al. 2021

Cancers

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Natural killer (NK) cells have shown great therapeutic potential against a wide range of cancers due to their pan-specific target recognition. Numerous reports indicate that NK cell immunotherapy is an effective therapeutic approach for treating hematological malignancies, but shows limited effects against solid tumors. In this study, several models of ovarian cancer (OC) were used to test the anti-cancer effects of NK cells derived from human peripheral blood mononuclear cells and expanded using a feeder cell-free expansion system (eNKs). The results show that eNKs exhibit potent inhibitory activity on tumor growth in different ovarian cancer xenograft mice (i.e., solid tumors, abdominal metastatic tumors, and ascites), importantly, in a dose-dependent manner. Moreover, adoptive transfer of eNKs resulted in significant reduction in ascites formation in OC peritoneal tumor models, and especially in reducing intraperitoneal ascites. We found that eNKs could migrate to the tumor site, retain their activity, and proliferate to maintain high cell counts in cutaneous xenograft mice. In addition, when increased the infusion with a high dose of 12 × 107 cells/mouse, Graft-versus-host disease could be induced by eNK. These data show that eNK cell immunotherapy could be a promising treatment strategy for ovarian cancers, including solid tumors and ascites.

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Section: Introductionmentioning

confidence: 99%

Anti-Tumor Activity of Expanded PBMC-Derived NK Cells by Feeder-Free Protocol in Ovarian Cancer

Chen

et al. 2021

Cancers

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“…[12,[26][27][28][29] To improve the activity of effector T cells against tumor cells, bispecific antibodies that simultaneously bind to T cells and tumor cells are undergoing clinical trials, [30][31][32] and similarly, nanoparticles conjugated to two types of ICB antibodies have been developed by several groups; [33][34][35] both of these approaches have the potential to promote engagement between T cells and tumor cells to augment antitumor immunity. [33,36,37] Although the efficacy of these strategies has been demonstrated in tumor-bearing mice or even in patients, a therapeutic strategy that could promote T cell infiltration and sustain their antitumor function at multiple levels remains rarely reported and highly desired.…”

Section: Discussionmentioning

confidence: 99%

Promoting the Recruitment, Engagement, and Reinvigoration of Effector T Cells via an Injectable Hydrogel with a Supramolecular Binding Capability for Cancer Immunotherapy

Zhu,

Jin,

Chen

et al. 2023

Advanced Materials

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T cells play a basic and key role in immunotherapy against solid tumors, and efficiently recruiting them into neoplastic foci and sustaining long‐term effector function are consistent goals that remain a critical challenge. Here, an injectable alginate‐based hydrogel with abundant β‐cyclodextrin (ALG‐βCD) sites was developed and intratumorally injected to recruit CCR9+CD8+ T cells (a subset of T cells with robust antitumor activity) via the trapped chemokine CCL25. In the meantime, an intravenously injected adamantane‐decorated anti‐PD1 antibody (Ad‐aPD1) would hitchhike on recruited CCR9+CD8+ T cells to achieve the improved intratumoral accumulation of Ad‐aPD1. Moreover, the Ad‐PD1 and Ad‐PDL1 antibodies were immobilized in the ALG‐βCD hydrogel through supramolecular host‐guest interactions of Ad and βCD, which facilitated engagement between CD8+ T cells and tumor cells and reinvigorated CD8+ T cells to avoid exhaustion. Base on this treatment strategy, T cell‐mediated anticancer activity was promoted at multiple levels, eventually achieving superior antitumor efficacy in both orthotopic and postsurgical B16‐F10 tumor models.This article is protected by copyright. All rights reserved

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“…The nano immunoswitch displayed a superior effect on retarding tumor growth and prolonging survival in murine melanoma and colon cancer models by increasing the density and functionality of tumor-specific CD8+ T cells. Based on similar concept, Wang and coworkers developed a universal nanoparticle platform (αFc -NP) in which anti-IgG antibody (αFc) was grafted onto aminated nanoparticles through sequential Schiff base production and reduction reaction 74 , 75 . The advantage of this nano-adaptor is that it could employ either FDA-granted mAbs or those under clinical trials in this formula through Fc-specific noncovalent interactions.…”

Section: Anti-tumor Strategies Targeting Pd-l1mentioning

confidence: 99%

Strategies targeting PD-L1 expression and associated opportunities for cancer combination therapy

Yin¹,

Chen²,

Chen³

et al. 2023

Theranostics

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Immunotherapy has achieved great success recently and opened a new avenue for anti-tumor treatment. Programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) are typical immune checkpoints that transmit coinhibitory signals, muting the host immunity. Monoclonal antibodies that block PD-1/PD-L1 axis have benefited many patients with different tumor diseases. However, the objective response rate is still unsatisfactory. In this review, we summarize three strategies targeting PD-L1 based on different forms of PD-L1 and various regulating mechanisms to enhance the therapeutic effect, including blockade of the interaction between PD-L1 and PD-1, downregulation of PD-L1 expression and degradation of mature PD-L1. Thereinto, we describe a variety of materials have been designed to target PD-L1, including antibodies, nanoparticle, peptide, aptamer, RNA, and small molecule. Additionally, we list the drugs with PD-L1 regulation capacity used in clinical and ongoing studies to explore other alternatives for targeting PD-L1 besides anti-PD-L1 monoclonal antibodies. Moreover, we discuss associated opportunities for cancer combination therapy with other modalities such as chemotherapy, radiotherapy, photodynamic therapy (PDT) and photothermal therapy (PTT), as these conventional or emerging modalities are capable of increasing the immune response of tumor cells by altering the tumor microenvironment (TME), and would display synergistic effect. At last, we give a brief summary and outlook regarding the research status and future prospect of immunotherapy.

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Dual-functional super bispecific nano-antibodies derived from monoclonal antibodies potentiate the antitumor effect of innate immune cells

Cited by 11 publications

References 41 publications

Anti-Tumor Activity of Expanded PBMC-Derived NK Cells by Feeder-Free Protocol in Ovarian Cancer

Anti-Tumor Activity of Expanded PBMC-Derived NK Cells by Feeder-Free Protocol in Ovarian Cancer

Promoting the Recruitment, Engagement, and Reinvigoration of Effector T Cells via an Injectable Hydrogel with a Supramolecular Binding Capability for Cancer Immunotherapy

Strategies targeting PD-L1 expression and associated opportunities for cancer combination therapy

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