Induced-T Cell Like NK Cellular Immunotherapy for Cancer Lack of MHC-I

Induced-T Cell Like NK Cellular Immunotherapy for Cancers That Are Lack of MHC-I Expression

T effector cells and NK cells have mutual compensatory killing functions on various of cancer types. For those cancers that have no available targets for CAR-T cell generations, we established potent T cell-like NK cells (ITNK) with a specific conversion protocol for the T cells from the patient, to perform anti-cancer therapy, especially for those cancers that are lack of MHC-I molecule expression. We have finished pre-clinical investigations for the ITNK or CAR-ITNK cell therapy and scheduled to start a clinical phase I study.

Study Overview

• Status: Recruiting
• Conditions: Anti-cancer Cell Immunotherapy; T Cell and NK Cell
• Intervention / Treatment: Biological: ITNK cell therapy

Detailed Description

One gene can be knockout of the T cells to produce a T-like NK cells which obtain killing function of both T effector cells and NK cells. We will collect appropriate patient's T cells, produce T-like NK cells (ITNK), and infuse the ITNK/CAR-ITNK cells back to the patients to treat various of cancers.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Zhenfeng Zhang, MD,PhD; Phone Number: +862034153532; Email: zhangzhf@gzhmu.edu.cn
• Study Contact Backup: Name: Peng Li, PhD; Email: lipeng@invivobio.com.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510260
      • Recruiting
      • The second Affiliated Hospital of Guangzhou Medical University
      • Contact: Zhenfeng Zhang, MD,PhD; Phone Number: +86-020-34153532; Email: zhangzhf@gzhmu.edu.cn
      • Sub-Investigator: Peng Li, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with advanced cancer, which express low or no MHC-I.
2. Life expectancy >12 weeks
3. Adequate heart,lung,liver,kidney function
4. Available autologous T cells
5. Informed consent explained to, understood by and signed by patient/guardian. 6. Patient/guardian given copy of informed consent.

Exclusion Criteria:

1. Had accepted gene therapy before;
2. Severe virus infection such as HBV,HCV,HIV,et al
3. Known HIV positivity
4. History of liver or other organ transplantation
5. Active infectious disease related to bacteria, virus,fungi,et al
6. Other severe diseases that the investigators consider not appropriate;
7. Pregnant or lactating women
8. Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day)
9. Other conditions that the investigators consider not appropriate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ITNK cell therapy group; Patient-originated and induced T-to-natural killer (ITNK) cells, will be administrated to kill tumor cells.	Biological: ITNK cell therapy; Infusion of ITNK/CAR-ITNK cells
Experimental: CAR-ITNK cell therapy group; Patient-originated and induced T-to-natural killer (ITNK) cells with CAR-engineered, will be administrated to kill tumor cells.	Biological: ITNK cell therapy; Infusion of ITNK/CAR-ITNK cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The safety and tolerance of the ITNK cell immunotherapy	A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the ITNK cells, which is irreversible, or life threatening or hematologic or non-hematologic Grade 3-5. Incidence of treatment-emergent adverse events will be calculated as standard methods.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Patients with best response as either complete remission or partial remission.	Response rates will be estimated as the percent of patients whose best response is either complete remission or partial remission by combining the data from the patients. To compare with historical data, a 95% confidence interval will be calculated for the response rate.	2 years

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Guangzhou Medical University
• Collaborators: Hunan Zhaotai Yongren Medical Innovation Co. Ltd.
• Investigators: Principal Investigator: Zhenfeng Zhang, MD, PhD, Second Affiliated Hospital of Guangzhou Medical University

Publications and helpful links

General Publications

• Li P, Burke S, Wang J, Chen X, Ortiz M, Lee SC, Lu D, Campos L, Goulding D, Ng BL, Dougan G, Huntly B, Gottgens B, Jenkins NA, Copeland NG, Colucci F, Liu P. Reprogramming of T cells to natural killer-like cells upon Bcl11b deletion. Science. 2010 Jul 2;329(5987):85-9. doi: 10.1126/science.1188063. Epub 2010 Jun 10.
• Jiang Z, Qin L, Tang Y, Liao R, Shi J, He B, Li S, Zheng D, Cui Y, Wu Q, Long Y, Yao Y, Wei Z, Hong Q, Wu Y, Mai Y, Gou S, Li X, Weinkove R, Norton S, Luo W, Feng W, Zhou H, Liu Q, Chen J, Lai L, Chen X, Pei D, Graf T, Liu X, Li Y, Liu P, Zhang Z, Li P. Human induced-T-to-natural killer cells have potent anti-tumour activities. Biomark Res. 2022 Mar 24;10(1):13. doi: 10.1186/s40364-022-00358-4.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2035

Study Registration Dates

• First Submitted: March 18, 2019
• First Submitted That Met QC Criteria: March 18, 2019
• First Posted (Actual): March 20, 2019

Study Record Updates

• Last Update Posted (Actual): June 26, 2024
• Last Update Submitted That Met QC Criteria: June 22, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Solid Tumor, ITNK, CAR-ITNK
• Other Study ID Numbers: ZZITNK-007

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No