Enhancing anti‐PD‐1 Immunotherapy by Nanomicelles Self‐Assembled from Multivalent Aptamer Drug Conjugates

Geng, Zhongmin; Wang, Lu; Liu, Ke; Liu, Jinyao; Tan, Weihong

doi:10.1002/anie.202102631

Cited by 58 publications

(46 citation statements)

References 66 publications

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“…Geng et al designed and synthesized an amphiphilic telomeric dimer, aptamer polyvalent drug conjugate (ApMDC). And described the use of ApMDC nanoparticles to enhance the antitumor reaction of α-PD1 immunotherapy with targeted chemotherapy to tumors (Geng et al, 2021). They established 4t1 (breast cancer cell) and h22 (hepatoma carcinoma cell) tumor-bearing mouse models and draw a conclusion that the increased antitumor immunity accelerated the therapeutic reaction of α-PD1.…”

Section: Aptamer Therapymentioning

confidence: 99%

PD-1/PD-L1 Checkpoint Inhibitors in Tumor Immunotherapy

et al. 2021

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Programmed death protein 1 (PD1) is a common immunosuppressive member on the surface of T cells and plays an imperative part in downregulating the immune system and advancing self-tolerance. Its ligand programmed cell death ligand 1 (PDL1) is overexpressed on the surface of malignant tumor cells, where it binds to PD1, inhibits the proliferation of PD1-positive cells, and participates in the immune evasion of tumors leading to treatment failure. The PD1/PDL1-based pathway is of great value in immunotherapy of cancer and has become an important immune checkpoint in recent years, so understanding the mechanism of PD1/PDL1 action is of great significance for combined immunotherapy and patient prognosis. The inhibitors of PD1/PDL1 have shown clinical efficacy in many tumors, for example, blockade of PD1 or PDL1 with specific antibodies enhances T cell responses and mediates antitumor activity. However, some patients are prone to develop drug resistance, resulting in poor treatment outcomes, which is rooted in the insensitivity of patients to targeted inhibitors. In this paper, we reviewed the mechanism and application of PD1/PDL1 checkpoint inhibitors in tumor immunotherapy. We hope that in the future, promising combination therapy regimens can be developed to allow immunotherapeutic tools to play an important role in tumor treatment. We also discuss the safety issues of immunotherapy and further reflect on the effectiveness of the treatment and the side effects it brings.

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Section: Aptamer Therapymentioning

confidence: 99%

PD-1/PD-L1 Checkpoint Inhibitors in Tumor Immunotherapy

et al. 2021

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“…To explore the generality of this strategy as a versatile platform for different aptamers, TLS11a was selected and the corresponding tumor model of H22 hepatocellular carcinoma was used to evaluate the effectiveness of conjugating aptamers to bacterial surface. [49,50] TLS11a based ApCB (T-ApCB) was synthesized similarly by co-incubating amino-functionalized TLS11a with VNP (Figure 6a). Details for the preparation of T-ApCB were described in the Supplementary Information.…”

Section: Versatility Of Apcbmentioning

confidence: 99%

Aptamer-assisted tumor localization of bacteria for enhanced biotherapy

Geng

Liu

et al. 2021

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Despite bacterial-mediated biotherapies have been widely explored for treating different types of cancer, their implementation has been restricted by severe side effects and low treatment efficacies, due largely to the absence of tumor-specific accumulation following administration. Here, the conjugation of aptamers to bacterial surface is described by a simple and cytocompatible amidation procedure, which can significantly promote the localization of bacteria in tumor site after systemic administration. The surface density of aptamers can be easily adjusted by varying feed ratio and the conjugation is able to increase the stability of anchored aptamers. Optimal bacteria conjugated with an average of 2.8 × 105 aptamers per cell present the highest specificity to tumor cells in vitro, separately generating near 2- and 5-times higher accumulation in tumor tissue at 12 and 60 hours compared to unmodified bacteria. In both 4T1 and H22 tumor-bearing mouse models, aptamer-conjugated attenuated Salmonella show strikingly enhanced antitumor efficacy, along with highly activated immune responses inside the tumor. This work demonstrates how bacterial behaviors can be tuned by surface conjugation and supports the potential of aptamer-conjugated bacteria for both targeted intratumoral localization and enhanced tumor biotherapy.

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“…[8][9][10] Recent efforts have been made to engineer the interspace of ligands to match the densities of target receptors on interfaces. [2,[11][12][13][14][15] However, target receptors on living cells are usually labile and unevenly distributed on lipid membranes, [16] posing difficulty in optimizing the multivalent binding efficiency. Thus far, the effect of molecular directionality on multivalent ligand-receptor interactions on living cells remains elusive, largely due to the difficulty in programming the ligand valence and directionality of the structures.…”

Section: Introductionmentioning

confidence: 99%

Directing Multivalent Aptamer‐Receptor Binding on the Cell Surface with Programmable Atom‐Like Nanoparticles

et al. 2022

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Multivalent interactions of biomolecules play pivotal roles in physiological and pathological settings. Whereas the directionality of the interactions is crucial, the state‐of‐the‐art synthetic multivalent ligand–receptor systems generally lack programmable approaches for orthogonal directionality. Here, we report the design of programmable atom‐like nanoparticles (aptPANs) to direct multivalent aptamer–receptor binding on the cell interface. The positions of the aptamer motifs can be prescribed on tetrahedral DNA frameworks to realize atom‐like orthogonal valence and direction, enabling the construction of multivalent molecules with fixed aptamer copy numbers but different directionality. These directional‐yet‐flexible aptPAN molecules exhibit the adaptability to the receptor distribution on cell surfaces. We demonstrate the high‐affinity tumor cell binding with a linear aptPAN oligomer (≈13‐fold improved compared to free aptamers), which leads to ≈50 % suppression of cell growth.

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Enhancing anti‐PD‐1 Immunotherapy by Nanomicelles Self‐Assembled from Multivalent Aptamer Drug Conjugates

Cited by 58 publications

References 66 publications

PD-1/PD-L1 Checkpoint Inhibitors in Tumor Immunotherapy

PD-1/PD-L1 Checkpoint Inhibitors in Tumor Immunotherapy

Aptamer-assisted tumor localization of bacteria for enhanced biotherapy

Directing Multivalent Aptamer‐Receptor Binding on the Cell Surface with Programmable Atom‐Like Nanoparticles

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