Strategies of Combination Drug Delivery for Immune Checkpoint Blockades

Ruan, Huitong; Bu, Lin‐Lin; Hu, Quanyin; Cheng, Hao; Lu, Weiyue; Gu, Zhen

doi:10.1002/adhm.201801099

Cited by 33 publications

(30 citation statements)

References 76 publications

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“…Despite the recent successes, the utilization of single antibodies is often limited and leads to poor treatment outcome. To achieve improved immune responses, the use of combination strategies for checkpoint inhibitors with other therapeutics may offer a stronger response against cancer as well as higher recovery rates (209, 210). PD-1 blockade was shown to enhance a specific antitumor efficacy of streptavidin-granulocyte-macrophage-CSF surface-modified bladder cancer stem cells vaccine (211).…”

Section: Therapeutic Strategies Targeting Csc and Their Microenvirementsmentioning

confidence: 99%

Therapeutic Strategies Targeting Cancer Stem Cells and Their Microenvironment

et al. 2019

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Cancer stem cells (CSCs) have been demonstrated in a variety of tumors and are thought to act as a clonogenic core for the genesis of new tumor growth. This small subpopulation of cancer cells has been proposed to help drive tumorigenesis, metastasis, recurrence and conventional therapy resistance. CSCs show self-renewal and flexible clonogenic properties and help define specific tumor microenvironments (TME). The interaction between CSCs and TME is thought to function as a dynamic support system that fosters the generation and maintenance of CSCs. Investigation of the interaction between CSCs and the TME is shedding light on the biologic mechanisms underlying the process of tumor malignancy, metastasis, and therapy resistance. We summarize recent advances in CSC biology and their environment, and discuss the challenges and future strategies for targeting this biology as a new therapeutic approach.

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Section: Therapeutic Strategies Targeting Csc and Their Microenvirementsmentioning

confidence: 99%

Therapeutic Strategies Targeting Cancer Stem Cells and Their Microenvironment

et al. 2019

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“…The small molecular compounds generally lack tumor specificity, which could induce severe side effects because of nonspecific drug distribution in the normal tissues. [ 24–26 ] Therefore, it is highly desirable to spatiotemporally codeliver multiple immune modulators to the tumor site for combination immunotherapy. Among the various nanovectors exploited for codelivery of multiple therapeutic regimens, supramolecular nanocomplexes have shown considerable potential for targeted drug delivery and cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

Supramolecular Prodrug Nanovectors for Active Tumor Targeting and Combination Immunotherapy of Colorectal Cancer

Hou

et al. 2020

Advanced Science

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Immunotherapy aiming to harness the exquisite power of the immune system has emerged as a crucial part of clinical cancer management. However, only a subset of cancer patients responds to current immunotherapy because of low immunogenicity of the tumor cells and immunosuppressive tumor microenvironment. Herein, host–guest prodrug nanovectors are reported for active tumor targeting and combating immune tolerance in tumors. The prodrug nanovectors are designed by integrating hyaluronic acid (HA) and reduction‐labile heterodimer of Pheophorbide A (PPa) and NLG919 into the supramolecular nanocomplexes, where PPa and NLG919 act as a photosensitizer and potent inhibitor of indoleamine 2,3‐dioxygenase 1 (IDO‐1), respectively. Meanwhile, HA is employed to achieve active tumor targeting by recognizing CD44 overexpressed on the surface of tumor cell membranes. Near infrared (NIR) laser irradiation triggers the release of reactive oxygen species to provoke antitumor immunogenicity and intratumoral infiltration of cytotoxic T lymphocytes (CTLs). Meanwhile, the immunosuppressive tumor microenvironment (ITM) is reversed by NLG919‐mediated IDO‐1 inhibition. Combination of photodynamic immunotherapy and IDO‐1 blockade efficiently eradicates CT26 colorectal tumors in the immunocompetent mice. The host–guest nanoplatform capable of eliciting effective antitumor immunity by inactivating inhibitory immune response can be applied to other immune modulators for improved cancer immunotherapy.

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“…Thus, numerous researchers are committed to finding superior alternatives for the present post-surgical operations [7][8][9]. Currently, antibody-mediated immunotherapy has attracted increasing interests since its characteristic of eradicating tumor cells through driving immune cells and cytokines with high specificity and efficiency [10][11][12]. Nevertheless, direct applications of the antibody as a drug for oncotherapy may result in serious cytokine storm.…”

Section: Introductionmentioning

confidence: 99%