GD2 Specific CAR and Interleukin-15 Expressing Autologous NKT Cells to Treat Children With Neuroblastoma

Summary

This research study combines two different ways of fighting cancer: antibodies and Natural Killer T cells (NKT). Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special white blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat patients with cancers. Investigators have found from previous research that they can put a new gene into T cells that will make them recognize cancer cells and kill them. In a previous clinical trial, investigators made artificial genes called a chimeric antigen receptors (CAR), from an antibody called 14g2a that recognizes GD2, a molecule found on almost all neuroblastoma cells (GD2-CAR). Investigators put these genes into the patients' own T cells and gave them back to patients that had neuroblastoma.

NKT cells are another special subgroup of white blood cells that can specifically go into tumor tissue of neuroblastoma. Inside the tumor, there are other white blood cells called macrophages which help the cancer cells to grow and recover from injury. NKT cells can specifically kill these macrophages and slow the tumor growth.

We will expand NKT cells and add GD2-specific chimeric antigen receptors to the cells. We think these cells might be better able to attack NB since they also work by destroying the macrophages that allows the tumor to grow. The chimeric antigen receptor will also contain a gene segment to make the NKT cells last longer. This gene segment is called CD28. In addition, to further improve the antitumor activity of the GINAKIT cells we added another gene expressing a molecule called Interleukin -15 (IL-15). The combination of these 3 components showed the most antitumor activity by CAR expressing NKT cells and improved these cells' survival in animal models. We also found that a medicine called ETANercept can slow down neuroblastoma growth, which might enhance the effects of the modified cells. In this part of our study, we aim to treat children with hard-to-treat neuroblastoma using these modified NKT cells along with ETANercept. Though ETANercept has been used to treat other diseases, such as rheumatoid arthritis in children, there is limited information about the safety, efficacy, and risk of ETANercept treatment in combination with cellular therapies.

GD2-CAR expressing NKTs have not been tested in patients so far. The purpose of this study is to find the largest effective and safe dose of GD2-CAR NKT cells (GINAKIT cells), to evaluate their effect on the tumor and how long they can be detected in the patient's blood and what affect they have on the patient's neuroblastoma.

Conditions

• Neuroblastoma

Interventions

GENETIC

GINAKIT Cells

Six dose levels of GINAKIT cells will be studied. Dosing will be based on the actual number of transduced cells. All doses are per m2. * Dose Level 1 = 3 x 10\^6 * Dose Level 2 = 1 x 10\^7 * Dose Level 3 = 3 x 10\^7 * Dose Level 4 = 1 x 10\^8 * Dose Level 5 = 3 x 10\^8 * Dose Level 6 = 1 x 10\^9

BIOLOGICAL

GINAKIT cells + Etanercept

Four dose levels of GINAKIT cells in combination of Etanercept will be studied. Dosing will be based on the actual number of transduced cells. All doses are per m2. * Combination Dose level 1: 3 x 10\^6 + Etanercept\* * Combination Dose level 2: 1 x 10\^7 + Etanercept\* * Combination Dose level 3: 3 x 10\^7 + Etanercept\* * Combination Dose level 4: 1 x 10\^8 + Etanercept

Sponsors & Collaborators

• Center for Cell and Gene Therapy, Baylor College of Medicine

  collaborator OTHER

• Baylor College of Medicine

  lead OTHER

Principal Investigators

• Gengwen Tian, MD · Baylor College of Medicine

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

1 Year

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-01-18

Primary Completion

2027-12-31

Completion

2040-08-10

FDA Drug

Yes

Countries

• United States

Study Locations