5 results on '"Linping Zhang"'
Search Results
2. Data from Intratumoral Injection of Clostridium novyi-NT Spores in Patients with Treatment-refractory Advanced Solid Tumors
- Author
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Mrinal M. Gounder, Khashayarsha Khazaie, Mary Varterasian, Brent Kreider, David Tung, Alexey A. Leontovich, Saurabh Saha, Linping Zhang, Ronald L. Korn, Jennifer L. Salstrom, Maria Miller, Amanda Collins, Gary DeCrescenzo, Ernest Trevino, Alice Weissfeld, Stephen B. Solomon, Jean Torrisi, Anjali Raina, Divya Sakamuri, Steven Y. Huang, Mark Klang, Daniel D. Karp, Sarina A. Piha-Paul, David S. Hong, Tyler Masters, Thorunn Helgason, Dale R. Shepard, Andrea Wang-Gillam, Ravi Murthy, Sanjay Goel, Abdulmohammad Pezeshki, Halle Huihong Zhang, and Filip Janku
- Abstract
Purpose:Intratumorally injected Clostridium novyi-NT (nontoxic; lacking the alpha toxin), an attenuated strain of C. novyi, replicates within hypoxic tumor regions resulting in tumor-confined cell lysis and inflammatory response in animals, which warrants clinical investigation.Patients and Methods:This first-in-human study (NCT01924689) enrolled patients with injectable, treatment-refractory solid tumors to receive a single intratumoral injection of C. novyi-NT across 6 dose cohorts (1 × 104 to 3 × 106 spores, 3+3 dose-escalation design) to determine dose-limiting toxicities (DLT), and the maximum tolerated dose.Results:Among 24 patients, a single intratumoral injection of C. novyi-NT led to bacterial spores germination and the resultant lysis of injected tumor masses in 10 patients (42%) across all doses. The cohort 5 dose (1 × 106 spores) was defined as the maximum tolerated dose; DLTs were grade 4 sepsis (n = 2) and grade 4 gas gangrene (n = 1), all occurring in three patients with injected tumors >8 cm. Other treatment-related grade ≥3 toxicities included pathologic fracture (n = 1), limb abscess (n = 1), soft-tissue infection (n = 1), respiratory insufficiency (n = 1), and rash (n = 1), which occurred across four patients. Of 22 evaluable patients, nine (41%) had a decrease in size of the injected tumor and 19 (86%) had stable disease as the best overall response in injected and noninjected lesions combined. C. novyi-NT injection elicited a transient systemic cytokine response and enhanced systemic tumor-specific T-cell responses.Conclusions:Single intratumoral injection of C. novyi-NT is feasible. Toxicities can be significant but manageable. Signals of antitumor activity and the host immune response support additional studies of C. novyi-NT in humans.
- Published
- 2023
3. Supplementary Legend from Intratumoral Injection of Clostridium novyi-NT Spores in Patients with Treatment-refractory Advanced Solid Tumors
- Author
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Mrinal M. Gounder, Khashayarsha Khazaie, Mary Varterasian, Brent Kreider, David Tung, Alexey A. Leontovich, Saurabh Saha, Linping Zhang, Ronald L. Korn, Jennifer L. Salstrom, Maria Miller, Amanda Collins, Gary DeCrescenzo, Ernest Trevino, Alice Weissfeld, Stephen B. Solomon, Jean Torrisi, Anjali Raina, Divya Sakamuri, Steven Y. Huang, Mark Klang, Daniel D. Karp, Sarina A. Piha-Paul, David S. Hong, Tyler Masters, Thorunn Helgason, Dale R. Shepard, Andrea Wang-Gillam, Ravi Murthy, Sanjay Goel, Abdulmohammad Pezeshki, Halle Huihong Zhang, and Filip Janku
- Abstract
Supplementary Legend
- Published
- 2023
4. Intratumoral Injection of Clostridium novyi-NT Spores in Patients with Treatment-refractory Advanced Solid Tumors
- Author
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Andrea Wang-Gillam, Ernest Trevino, Sarina Anne Piha-Paul, Halle H. Zhang, Khashayarsha Khazaie, Amanda Collins, Tyler Masters, Mark Klang, Thorunn Helgason, Daniel D. Karp, Sanjay Goel, David Tung, Ronald L. Korn, Alexey A. Leontovich, Brent Kreider, Filip Janku, Mary Varterasian, Saurabh Saha, Divya Sakamuri, Maria Miller, David S. Hong, Anjali Raina, Jennifer L. Salstrom, Jean Torrisi, Decrescenzo Gary A, Alice S. Weissfeld, Linping Zhang, Dale R. Shepard, Abdul Mohammad Pezeshki, Stephen B. Solomon, Mrinal M. Gounder, Steven Y. Huang, and Ravi Murthy
- Subjects
0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Pathologic fracture ,business.industry ,medicine.disease ,Gastroenterology ,Rash ,Sepsis ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immune system ,Oncology ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Clostridium Novyi-NT Spores ,medicine.symptom ,Respiratory system ,business ,Abscess ,Gas gangrene - Abstract
Purpose: Intratumorally injected Clostridium novyi-NT (nontoxic; lacking the alpha toxin), an attenuated strain of C. novyi, replicates within hypoxic tumor regions resulting in tumor-confined cell lysis and inflammatory response in animals, which warrants clinical investigation. Patients and Methods: This first-in-human study (NCT01924689) enrolled patients with injectable, treatment-refractory solid tumors to receive a single intratumoral injection of C. novyi-NT across 6 dose cohorts (1 × 104 to 3 × 106 spores, 3+3 dose-escalation design) to determine dose-limiting toxicities (DLT), and the maximum tolerated dose. Results: Among 24 patients, a single intratumoral injection of C. novyi-NT led to bacterial spores germination and the resultant lysis of injected tumor masses in 10 patients (42%) across all doses. The cohort 5 dose (1 × 106 spores) was defined as the maximum tolerated dose; DLTs were grade 4 sepsis (n = 2) and grade 4 gas gangrene (n = 1), all occurring in three patients with injected tumors >8 cm. Other treatment-related grade ≥3 toxicities included pathologic fracture (n = 1), limb abscess (n = 1), soft-tissue infection (n = 1), respiratory insufficiency (n = 1), and rash (n = 1), which occurred across four patients. Of 22 evaluable patients, nine (41%) had a decrease in size of the injected tumor and 19 (86%) had stable disease as the best overall response in injected and noninjected lesions combined. C. novyi-NT injection elicited a transient systemic cytokine response and enhanced systemic tumor-specific T-cell responses. Conclusions: Single intratumoral injection of C. novyi-NT is feasible. Toxicities can be significant but manageable. Signals of antitumor activity and the host immune response support additional studies of C. novyi-NT in humans.
- Published
- 2021
5. Abstract LB-B15: A novel PI3K gamma isoform selective small molecule kinase inhibitor demonstrates single agent anti-tumor activity and enhanced combination activity with checkpoint blockade in syngeneic mouse models of cancer
- Author
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Cameron Stuver Moody, Wojciech Dworakowski, Suvarna Khare-Pandit, Sudipta Mahajan, Jon H. Come, Alex Aronov, Saurabh Saha, Arnaud LeTiran, Thomas Hoock, Linping Zhang, Michael J. Boyd, Veronique Damagnez, Joseph Prezioso, Harwin O'Dowd, Xiaoyan M. Zhang, and Setu Roday
- Subjects
Cancer Research ,Tumor microenvironment ,Myeloid ,biology ,Chemistry ,Kinase ,Lymphocyte ,Cancer ,medicine.disease ,medicine.anatomical_structure ,Oncology ,Immunology ,biology.protein ,medicine ,Cancer research ,Antibody ,CD8 ,PI3K/AKT/mTOR pathway - Abstract
Immune checkpoint inhibitors have generated impressive clinical responses, however, a number of patients and cancer types remain resistant to checkpoint blockade. Immunosuppressive cells such as Tregs and MDSCs in the tumor microenvironment are hypothesized to mediate this resistance. The gamma (γ) isoform of PI3K has long been known to modulate myeloid and lymphocyte cell migration and function, including trafficking of monocytic and granulocytic cells into inflamed tissues such as tumors. Here we report the identification and characterization of BVD-723, a PI3Kγ selective small molecule kinase inhibitor which demonstrated single agent and enhanced combination anti-tumor activity[xx]with either an anti-PD-1 or anti-CTLA-4 antibody. In a mouse syngeneic colon cancer model,[xx]BVD-723 in combination with anti-PD-1 or anti-CTLA-4 resulted in complete regression[xx]of tumors in 35% (7/20) and 60% (12/20) of animals treated with each antibody respectively [versus 0% (0/20) and 5% (1/20) with either antibody alone]. Interestingly, the anti-tumor activity was coupled with a decrease in tumor infiltrating Tregs, granulocytic MDSCs, CD4+ T cells and an increase in the CD8+/Treg ratio, suggesting that inhibition of PI3Kγ by BVD-723 promotes immune-reactivation in the tumor microenvironment. Additionally, BVD-723 demonstrated potent synergy with an anti-PD-1 antibody in a syngeneic mouse model of lymphoma. Single agent BVD-723 activity was also observed in syngeneic mouse models of pancreas, colon, lymphoma and bladder cancers. Results from completed safety pharmacology, toxicology and in vivo efficacy studies support clinical evaluation of BVD-723[xx]as a monotherapy or in combination with the checkpoint inhibitors in cancer.[xx] Citation Format: Saurabh Saha, Linping Zhang, Thomas Hoock, Alex Aronov, Sudipta Mahajan, Michael Boyd, Jon Come, Veronique Damagnez, Wojciech Dworakowski, Suvarna Khare-Pandit, Arnaud LeTiran, Cameron Moody, Harwin O'Dowd, Joseph Prezioso, Setu Roday, Xiaoyan M. Zhang. A novel PI3K gamma isoform selective small molecule kinase inhibitor demonstrates single agent anti-tumor activity and enhanced combination activity with checkpoint blockade in syngeneic mouse models of cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr LB-B15.
- Published
- 2015
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