2. Academic Validation
  3. Reprogramming tumor microenvironment with precise photothermal therapy by calreticulin nanobody-engineered probiotics

Reprogramming tumor microenvironment with precise photothermal therapy by calreticulin nanobody-engineered probiotics

  • Biomaterials. 2024 Sep 4:314:122809. doi: 10.1016/j.biomaterials.2024.122809.
Liuhai Zheng 1,  Huifang Wang 1,  Xiaoru Zhong 2,  Lin Jia 3,  Guangwei Shi 4,  Chongzhi Bai 5,  Runwei Yang 6,  Zhenhui Huang 3,  Yuke Jiang 7,  Jinxi Wei 2,  Zhiyu Dong 2,  Jiexuan Li 2,  Ying Long 2,  Lingyun Dai 8,  Zhijie Li 9,  Chunbo Chen 10,  Jigang Wang 11
Affiliations

Affiliations

  • 1 Department of Critical Care Medicine, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, China; Post-doctoral Scientific Research Station of Basic Medicine, Jinan University, Guangzhou, Guangdong, 510632, China.
  • 2 Department of Hyperbaric Oxygen Medicine, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University), Shenzhen, Guangdong, 518020, China.
  • 3 College of Pharmacy, Shenzhen Technology University, Shenzhen, 518118, China.
  • 4 Department of Critical Care Medicine, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, China; Department of Neurosurgery & Medical Research Center, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Foshan, 528399, China.
  • 5 Central Laboratory, Shanxi Province Hospital of Traditional Chinese Medicine, Taiyuan, 030012, China.
  • 6 Department of Neurosurgery & Medical Research Center, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Foshan, 528399, China.
  • 7 Department of Critical Care Medicine, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, China; State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China; State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng, 475004, China.
  • 8 Department of Critical Care Medicine, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, China. Electronic address: lingyun.dai@outlook.com.
  • 9 Department of Hyperbaric Oxygen Medicine, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University), Shenzhen, Guangdong, 518020, China. Electronic address: li.zhijie@szhospital.com.
  • 10 Department of Critical Care Medicine, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, China. Electronic address: gghccm@163.com.
  • 11 Department of Critical Care Medicine, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, China; State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China; State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng, 475004, China. Electronic address: jgwang@icmm.ac.cn.
PMID: 39303415 DOI: 10.1016/j.biomaterials.2024.122809
Abstract

Targeted therapies have revolutionized traditional Cancer treatments by precisely targeting tumor cells, enhancing efficacy and safety. Despite this advancement, the proportion of Cancer patients eligible for such therapies remains low due to the absence of suitable targets. Here, we investigate whether the translocation of the immunogenic cell death (ICD) marker calreticulin (CALR) from the endoplasmic reticulum (ER) to the cell surface following ICD induction can serve as a target for targeted therapies. To target CALR, a nanobody Nb215 identified from a naïve VHH phage library with high binding affinity to both human and mouse CALR was employed to engineer probiotic EcN 1917. Our results demonstrated that CALR nanobody-modified EcN-215 coupled with the photothermal dye indocyanine green (ICG) was able to exert NIR-II imaging-guide photothermal therapy (PTT). Moreover, PTT with EcN-215/ICG can reshape the tumor microenvironment by enhancing the infiltration of CD45+CD3+ T cells and CD11b+F4/80+ macrophages. Furthermore, the antitumor activity of CALR-targeted EcN-215/ICG is synergistically enhanced by blocking CD47-SIRPα axis. Collectively, our study provides a proof of concept for CALR-targeted therapy. Given that CALR translocation can be induced by various Anticancer therapies across numerous tumor cell lines, CALR-targeted therapies hold promise as a novel approach for treating multiple types of cancers.

Keywords

CALR; Immunogenic cell death; Nanobody; Photothermal therapy; Targeted therapies.

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