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

Study Overview
=================
Brief Summary
-----------------
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 cell therapy and scheduled to start a clinical phase I study.

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 cells back to the patients to treat various of cancers.

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

Conditions
-----------------
Anti-cancer Cell Immunotherapy, T Cell and NK Cell

Intervention / Treatment
-----------------
* Biological: NK cell therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with advanced cancer, which express low or no MHC-I. Life expectancy >12 weeks Adequate heart,lung,liver,kidney function Available autologous T cells Informed consent explained to, understood by and signed by patient/guardian. 6. Patient/guardian given copy of informed consent. Exclusion Criteria: Had accepted gene therapy before; Severe virus infection such as HBV,HCV,HIV,et al Known HIV positivity History of liver or other organ transplantation Active infectious disease related to bacteria, virus,fungi,et al Other severe diseases that the investigators consider not appropriate; Pregnant or lactating women Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day) Other conditions that the investigators consider not appropriate.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: itNK cell therapy group<br>Patient-originated and induced T-to-natural killer (ITNK) cells, will be administrated to kill tumor cells. | Biological: NK cell therapy<br>* Infusion of itNK cells<br>|

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 |