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Co-targeting CD47 and VEGF elicited potent anti-tumor effects in gastric cancer.
Zhang, Kaiqi; Xu, Yuan; Chang, Xusheng; Xu, Caili; Xue, Wenjing; Ding, Dan; Nie, Mingming; Cai, Hui; Xu, Jun; Zhan, Lu; Han, Jiangbo; Cai, Tiancai; Ju, Dianwen; Feng, Li; Zhang, Xuyao; Yin, Kai.
Afiliación
  • Zhang K; Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
  • Xu Y; Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
  • Chang X; Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
  • Xu C; Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, School of Pharmacy, Fudan University, Shanghai, 201203, China.
  • Xue W; Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, School of Pharmacy, Fudan University, Shanghai, 201203, China.
  • Ding D; Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
  • Nie M; Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
  • Cai H; Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
  • Xu J; Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
  • Zhan L; Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
  • Han J; Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
  • Cai T; Department of Sanatorium and Nursing Section, Xiamen Special Service Health Center, Xiamen, 361005, China.
  • Ju D; Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, School of Pharmacy, Fudan University, Shanghai, 201203, China.
  • Feng L; Department of Endoscopy Center, Minhang Hospital, Fudan University, 170 Xinsong Road, Shanghai, 201199, China. feng_li@fudan.edu.cn.
  • Zhang X; Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, School of Pharmacy, Fudan University, Shanghai, 201203, China. xuyaozhang@fudan.edu.cn.
  • Yin K; Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China. kyin67@smmu.edu.cn.
Cancer Immunol Immunother ; 73(4): 75, 2024 Mar 27.
Article en En | MEDLINE | ID: mdl-38532108
ABSTRACT

BACKGROUND:

CD47, serving as an intrinsic immune checkpoint, has demonstrated efficacy as an anti-tumor target in hematologic malignancies. Nevertheless, the clinical relevance of CD47 in gastric cancer and its potential as a therapeutic target remains unclear.

METHODS:

The expression of CD47 in clinical gastric cancer tissues was assessed using immunohistochemistry and Western blot. Patient-derived cells were obtained from gastric cancer tissues and co-cultured with macrophages derived from human peripheral blood mononuclear cells. Flow cytometry analyses were employed to evaluate the rate of phagocytosis. Humanized patient-derived xenografts (Hu-PDXs) models were established to assess the efficacy of anti-CD47 immunotherapy or the combination of anti-CD47 and anti-VEGF therapy in treating gastric cancer. The infiltrated immune cells in the xenograft were analyzed by immunohistochemistry.

RESULTS:

In this study, we have substantiated the high expression of CD47 in gastric cancer tissues, establishing a strong association with unfavorable prognosis. Through the utilization of SIRPα-Fc to target CD47, we have effectively enhanced macrophage phagocytosis of PDCs in vitro and impeded the growth of Hu-PDXs. It is noteworthy that anti-CD47 immunotherapy has been observed to sustain tumor angiogenic vasculature, with a positive correlation between the expression of VEGF and CD47 in gastric cancer. Furthermore, the successful implementation of anti-angiogenic treatment has further augmented the anti-tumor efficacy of anti-CD47 therapy. In addition, the potent suppression of tumor growth, prevention of cancer recurrence after surgery, and significant prolongation of overall survival in Hu-PDX models can be achieved through the simultaneous targeting of CD47 and VEGF using the bispecific fusion protein SIRPα-VEGFR1 or by combining the two single-targeted agents.

CONCLUSIONS:

Our preclinical studies collectively offer substantiation that CD47 holds promise as a prospective target for gastric cancer, while also highlighting the potential of anti-angiogenic therapy to enhance tumor responsiveness to anti-CD47 immunotherapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Gástricas / Neoplasias Límite: Animals / Humans Idioma: En Revista: Cancer Immunol Immunother Asunto de la revista: ALERGIA E IMUNOLOGIA / NEOPLASIAS / TERAPEUTICA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Gástricas / Neoplasias Límite: Animals / Humans Idioma: En Revista: Cancer Immunol Immunother Asunto de la revista: ALERGIA E IMUNOLOGIA / NEOPLASIAS / TERAPEUTICA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania