CAR NK Cell Therapy for Kidney Cancer

Overseen By Andrew C Johns, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must be taking: ICI, TKI

Must not be taking: Anticancer agents, Immunosuppressive therapy

Disqualifiers: Hepatitis B/C, HIV, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cancer therapy called TGFBR-2 KO CD70 CAR NK cell therapy. The goal is to determine if these modified immune cells can treat advanced kidney cancer that cannot be surgically removed. The trial consists of two phases: one to identify the optimal dose and another to expand the dose to more participants. It suits individuals whose kidney cancer has spread or cannot be removed, have had previous treatments fail, and have CD70 protein present in their tumors. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that participants stop taking certain medications, such as cytotoxic chemotherapy, tyrosine kinase inhibitors, and other targeted therapies, at least 2 weeks before starting the trial. Additionally, participants cannot use other investigational or anticancer agents during the trial.

Is there any evidence suggesting that TGFBR-2 KO CD70 CAR NK cell therapy is likely to be safe for humans?

Research shows that TGFBR-2 KO CD70 CAR NK cells, a type of cancer treatment, are still under investigation for safety. Data on patient tolerance for this treatment is not yet available. However, similar CAR NK cell therapies have shown safety in past studies, without major side effects such as nerve problems or severe reactions.

As a Phase 1 trial, the primary goal is to assess the treatment's safety. Researchers closely monitor for any side effects. Although specific safety data for TGFBR-2 KO CD70 CAR NK cells is not yet available, these early trials are designed to quickly identify any potential issues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about TGFBR-2 KO CD70 CAR NK Cells because they represent a novel approach to treating kidney cancer. Unlike traditional treatments like surgery, radiation, or chemotherapy, this therapy uses genetically modified natural killer (NK) cells to directly target and destroy cancer cells. The CAR NK cells are engineered to knock out the TGFBR-2 gene, which may enhance their ability to fight tumors by avoiding suppression from the cancer's environment. This innovative mechanism could lead to more effective treatment with potentially fewer side effects, offering new hope for patients with kidney cancer.

What evidence suggests that TGFBR-2 KO CD70 CAR NK cell therapy might be an effective treatment for kidney cancer?

Research has shown that a new type of cell therapy, TGFBR-2 KO CD70 CAR NK cells, targets kidney cancer cells that other treatments cannot effectively reach. These cells possess a unique ability to locate and destroy cancer cells. Early lab tests demonstrated their capacity to shrink tumors by recognizing specific features on cancer cells. Although studies in humans remain in the early stages, this approach aims to enhance the immune system’s ability to fight cancer. This innovative therapy offers hope for treating difficult-to-treat kidney cancers. Participants in this trial will join either the dose-expansion phase or the dose-optimization phase to evaluate the therapy's effectiveness and safety. ^{1 3 4 6 7}

Who Is on the Research Team?

Andrew C Johns, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for people with advanced clear cell renal cell carcinoma (kidney cancer) that hasn't responded to other treatments. Participants must be in good physical condition and have adequate organ function.

Inclusion Criteria

It has been over 3 months since my last cell therapy for cancer.

Able to provide written informed consent

All male and female Participants who are able to have children must practice effective birth control while on study therapy and for up to 3 months post completion of study therapy

Exclusion Criteria

I am HIV positive.

Active autoimmune disease within 12 months of enrollment

I have active hepatitis B or C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-optimization

Participants receive varying doses of TGFBR-2 KO CD70 CAR NK cells to determine the optimal cell dose

8-12 weeks

Dose-expansion

Participants receive the optimal dose of TGFBR-2 KO CD70 CAR NK cells to further assess safety and efficacy

8-12 weeks

Follow-up

Participants are monitored for safety, tolerability, and antitumor activity after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• TGFBR-2 KO CD70 CAR NK Cells

Trial Overview The study tests a new therapy called TGFBR-2 KO CD70 CAR NK cells, combined with lymphodepleting chemotherapy drugs like Cyclophosphamide and Fludarabine, as well as Dexamethasone to manage side effects.

How Is the Trial Designed?

Group I: Dose-optimization phase Experimental Treatment 5 Interventions

Group II: Dose-expansion phase Experimental Treatment 5 Interventions

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07072234

Phase I Study of Allogeneic Transforming Growth Factor ... Although the clinical benefit of TGFBR-2 KO CD70 CAR NK cells has not yet been established in ccRCC, the intent of offering this treatment is to ...

2. patlynk.com patlynk.com/trial/NCT07072234

TGFBR-2 KO CD70 CAR NK Cells for Advanced Clear ... This study focuses on a new treatment for advanced clear cell renal cell carcinoma, a type of kidney cancer that has not responded well to other treatments.

3. withpower.com withpower.com/trial/phase-1-adenocarcinoma-clear-cell-2026-2d8c5

CAR NK Cell Therapy for Kidney Cancer This Phase 1 medical study run by M.D. Anderson Cancer Center is evaluating whether TGFBR-2 KO CD70 CAR NK Cells will have tolerable side effects & efficacy ...

4. researchgate.net researchgate.net/publication/379653942_CD70-Targeted_Allogeneic_CAR_T-Cell_Therapy_for_Advanced_Clear_Cell_Renal_Cell_Carcinoma

(PDF) CD70-Targeted Allogeneic CAR T-Cell Therapy for ... Chimeric antigen receptor (CAR)-NK cells can eliminate tumors not only through the ability of the CAR molecule to recognize antigen expressed ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11882582/

NK cells in renal cell carcinoma and its implications for ... Treating RCC cells with NK-CD24-CAR cells could lead to decreased cell viability and induction of apoptosis, especially in CD24+ tumor cells ( ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1936523325002864

CD70-targeted CAR-T/NK therapy: Rationale, advances, ... No clinical data exist yet, and Phase I trials (e.g., NCT05518253) will determine safety and feasibility [56]. According to Yang et al., CAR-T cells targeting ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12162902/

CAR-NK cells: harnessing the power of natural killers for ... Of note, in agreement with the results from the previous studies, the safety profile was favourable, with neither neurotoxic nor systemic side effects (51).