&lt;p&gt;Potential New Cancer Immunotherapy: Anti-CD47-SIRPα Antibodies&lt;/p&gt;

Lu, Quansheng; Chen, Xi; Wang, Shan; Lu, Yu; Yang, Chunsheng; Jiang, Guan

doi:10.2147/ott.s249822

Cited by 23 publications

(20 citation statements)

References 59 publications

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“…Different types of cancer patients were studied in these clinical trials, including 29 trials in solid tumor (ST) including gastric cancer (GC), head and neck squamous cell carcinoma (HNSC), and leiomyosarcoma (LMS), 14 trials in hematological malignancies including non-Hodgkin's lymphoma (NHL), AML, MDS, MM and chronic myeloid leukemia (CML), as well as 3 trials in both solid tumors and hematological malignancies. Among these clinical trials, different anti-CD47 mAbs were investigated with various strategies [ 47 ]. The types of mAbs and its MOAs were quite diverse (Table 1 , 2 ).…”

Section: The Clinical Development Of Cd47 Mabs In the Usamentioning

confidence: 99%

Targeting CD47 for cancer immunotherapy

et al. 2021

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Much progress has been made in targeting CD47 for cancer immunotherapy in solid tumors (ST) and hematological malignancies. We summarized the CD47-related clinical research and analyzed the research trend both in the USA and in China. As of August 28, 2021, there are a total 23 related therapeutic agents with 46 clinical trials in the NCT registry platform. Among these trials, 29 are in ST, 14 in hematological malignancies and 3 in both solid tumor and hematological malignancy. The ST include gastric cancer, head and neck squamous cell carcinoma and leiomyosarcoma, while the hematological malignancies include non-Hodgkin's lymphoma, acute myeloid leukemia, myelodysplastic syndrome, multiple myeloma and chronic myeloid leukemia. Majority of the CD47-related clinical trials are at the early phases, such as 31 at phase I, 14 at phase II and 1 at phase III in the USA and 9, 6, 1, in China, respectively. The targets and spectrums of mechanism of action include 26 with mono-specific and 20 with bi-specific targets in the USA and 13 with mono-specific and 3 with bi-specific targets in China. The new generation CD47 antibodies have demonstrated promising results, and it is highly hopeful that some candidate agents will emerge and make into clinical application to meet the urgent needs of patients.

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Section: The Clinical Development Of Cd47 Mabs In the Usamentioning

confidence: 99%

Targeting CD47 for cancer immunotherapy

et al. 2021

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“…Surface CRT is able to induce an “eat me” signal to phagocytes [ 307 ], increasing their activity along with DC maturation and antigen-presenting function [ 308 ]. The calreticulin effect is antagonized by the interaction of CD47 present on the tumor cell membrane with SIRP-alpha α located on macrophages and DC [ 309 ]), generating a “do not eat me” message in target phagocytes [ 310 ]. Increased expression of HSP90 and HSP70 by ICD inducers [ 247 ].…”

Section: Figurementioning

confidence: 99%

Abscopal Effect and Drug-Induced Xenogenization: A Strategic Alliance in Cancer Treatment?

Franzese

Torino

Giannetti

et al. 2021

IJMS

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The current state of cancer treatment is still far from being satisfactory considering the strong impairment of patients’ quality of life and the high lethality of malignant diseases. Therefore, it is critical for innovative approaches to be tested in the near future. In view of the crucial role that is played by tumor immunity, the present review provides essential information on the immune-mediated effects potentially generated by the interplay between ionizing radiation and cytotoxic antitumor agents when interacting with target malignant cells. Therefore, the radiation-dependent abscopal effect (i.e., a biological effect of ionizing radiation that occurs outside the irradiated field), the influence of cancer chemotherapy on the antigenic pattern of target neoplastic cells, and the immunogenic cell death (ICD) caused by anticancer agents are the main topics of this presentation. It is widely accepted that tumor immunity plays a fundamental role in generating an abscopal effect and that anticancer drugs can profoundly influence not only the host immune responses, but also the immunogenic pattern of malignant cells. Remarkably, several anticancer drugs impact both the abscopal effect and ICD. In addition, certain classes of anticancer agents are able to amplify already expressed tumor-associated antigens (TAA). More importantly, other drugs, especially triazenes, induce the appearance of new tumor neoantigens (TNA), a phenomenon that we termed drug-induced xenogenization (DIX). The adoption of the abscopal effect is proposed as a potential therapeutic modality when properly applied concomitantly with drug-induced increase in tumor cell immunogenicity and ICD. Although little to no preclinical or clinical studies are presently available on this subject, we discuss this issue in terms of potential mechanisms and therapeutic benefits. Upcoming investigations are aimed at evaluating how chemical anticancer drugs, radiation, and immunotherapies are interacting and cooperate in evoking the abscopal effect, tumor xenogenization and ICD, paving the way for new and possibly successful approaches in cancer therapy.

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“…It was reported that 90% of orally bioavailable non-CNS drugs had a PSA below 120 Å 2 , and the criterion was dropped to 80 Å 2 for CNS drugs. 21 QSAR models can also serve as a filter in VS. [22][23][24][25] A QSAR-based filter is widely applied in the drug lead optimization phase.…”

Section: Virtual Screening Filtersmentioning

confidence: 99%

Development and Testing of Druglike Screening Libraries

Wang

Xie

2018

J. Chem. Inf. Model.

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Although significant advances in experimental high throughput screening (HTS) have been made for drug lead identification, in silico virtual screening (VS) is indispensable owing to its unique advantage over experimental HTS, target-focused, cheap, and efficient, albeit its disadvantage of producing false positive hits. For both experimental HTS and VS, the quality of screening libraries is crucial and determines the outcome of those studies. In this paper, we first reviewed the recent progress on screening library construction. We realized the urgent need for compiling high-quality screening libraries in drug discovery. Then we compiled a set of screening libraries from about 20 million druglike ZINC molecules by running fingerprint-based similarity searches against known drug molecules. Lastly, the screening libraries were objectively evaluated using 5847 external actives covering more than 2000 drug targets. The result of the assessment is very encouraging. For example, with the Tanimoto coefficient being set to 0.75, 36% of external actives were retrieved and the enrichment factor was 13. Additionally, drug target family specific screening libraries were also constructed and evaluated. The druglike screening libraries are available for download from https://mulan.pharmacy.pitt.edu.

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<p>Potential New Cancer Immunotherapy: Anti-CD47-SIRPα Antibodies</p>

Cited by 23 publications

References 59 publications

Targeting CD47 for cancer immunotherapy

Targeting CD47 for cancer immunotherapy

Abscopal Effect and Drug-Induced Xenogenization: A Strategic Alliance in Cancer Treatment?

Development and Testing of Druglike Screening Libraries

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