NK Cell Therapy + Chemotherapy for Advanced Kidney, Lung, or Bone Cancer

Overseen By David Hong, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anticancer agents, Immunosuppressives

Disqualifiers: Infections, Autoimmune disease, Neurological disorders, others

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

Compensation: Varies

Number of Visits: Unknown

50 Participants Needed

Trial Summary

What is the purpose of this trial?

To find a recommended dose of donated NK cells that can be given with lymphodepleting chemotherapy to patients with advanced renal cell carcinoma, mesothelioma, or osteosarcoma. The effects of this therapy will also be studied.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as cytotoxic chemotherapy, tyrosine kinase inhibitors, or other targeted therapies, at least 2 weeks before starting the trial's lymphodepleting chemotherapy. If you are on systemic steroid therapy, you may need to stop or adjust your dose, unless it's a low dose or specific type like topical or inhaled steroids.

What data supports the effectiveness of the treatment NK Cell Therapy + Chemotherapy for Advanced Kidney, Lung, or Bone Cancer?

Research shows that NK cells engineered with chimeric antigen receptors (CARs) and interleukin-15 (IL-15) have demonstrated strong anti-tumor activity in preclinical studies, particularly against leukemia and lymphoma. These engineered NK cells can be produced from cord blood and have shown potential as a safe and effective 'off-the-shelf' cancer treatment, offering advantages over traditional CAR-T cell therapies. ^{1 2 3 4 5}

Is NK cell therapy safe for humans?

Research shows that NK cell therapy, especially using engineered NK cells from cord blood, is generally safe for humans. These cells do not cause graft-versus-host disease (a condition where donor cells attack the recipient's body) and have built-in safety measures to limit toxicity. ^{1 2 3 4 6}

How is the NK Cell Therapy + Chemotherapy treatment different from other treatments for advanced kidney, lung, or bone cancer?

This treatment uses engineered natural killer (NK) cells from cord blood, which are modified to express IL-15 and a chimeric antigen receptor (CAR) to target cancer cells. Unlike traditional therapies, these NK cells can be used 'off-the-shelf' without causing severe side effects like graft-versus-host disease, making them a novel and potentially safer option for cancer treatment. ^{1 2 7 8 9}

Research Team

David Hong, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults aged 18-80 with advanced renal cell carcinoma, mesothelioma, or osteosarcoma showing CD70 expression can join. They must have proper organ function and agree to birth control use. Exclusions include serious medical conditions, recent heart issues or major surgery, other cancer treatments or investigational drugs within specific time frames.

Inclusion Criteria

I've had targeted radiation before chemo, but still have untreated cancer areas.

I can do all my daily activities without help.

My cancer shows high CD70 levels in tests.

Exclusion Criteria

I do not have any serious health conditions that could make the treatment unsafe for me.

I have active hepatitis B or C, or HIV with a detectable viral load.

I have symptoms or uncontrolled issues in my brain or spinal cord.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy prior to NK cell infusion

1-2 weeks

NK Cell Infusion

Participants receive CAR.70/IL15-transduced cord blood-derived NK cells at assigned dose levels

1 week

Follow-up

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

4-8 weeks

Treatment Details

Interventions

• CAR.70/IL15-transduced CB-derived NK cells
• Cyclophosphamide
• Fludarabine phosphate

Trial Overview The trial is testing the safety and dosage of CAR.70/IL15-transduced CB-derived NK cells combined with lymphodepleting chemotherapy (Fludarabine phosphate and Cyclophosphamide) in patients with certain advanced cancers to see how well they work together.

Participant Groups

Group I: Chemotherapy and NK Cell Infusion Experimental Treatment 3 Interventions

Participants will be assigned to a dose level of NK cells. A computer will decide by chance which of the dose level you will receive, and this will not be based on the doctor's or patient's decision. Up to 5 dose levels of NK cells will be tested. Each new patient will receive a different dose. If any dose shows to be not tolerable, this dose and the higher doses will not be given anymore.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

CAR-T cell therapy has transformed treatment for relapsed or refractory B-cell cancers, but it faces challenges such as variable T cell quality, high costs, and potential toxicities.

Natural Killer (NK) cells present a promising alternative for cancer treatment, as they can be used in allogeneic settings with fewer side effects, and recent advancements in CAR-NK cell engineering enhance their effectiveness against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Allogeneic CAR-NK cells: A promising alternative to autologous CAR-T cells - State of the art, sources of NK cells, limits and perspectives]. Nguyen, S., Lacan, C., Roos-Weil, D.[2021]

Engineered cord blood-derived natural killer (NK) cells, modified with CAR-CD19 and IL-15, showed effective targeting and killing of leukemia cells in laboratory tests and improved survival in a mouse model of lymphoma.

This approach not only enhances the efficacy of NK cells in treating cancers but also includes a safety mechanism (the iC9 suicide gene) to eliminate the cells if necessary, reducing the risk of adverse effects like graft-versus-host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity. Liu, E., Tong, Y., Dotti, G., et al.[2021]

CAR-modified Natural Killer (NK) cells present a promising alternative to CAR T cells for cancer treatment due to their MHC-independency, shorter lifespan, and potential for off-the-shelf use, making them a flexible option for targeting tumors.

The review highlights ongoing challenges in enhancing the efficacy and safety of CAR NK cells, particularly in solid tumors, and discusses strategies to improve their persistence and function in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor-Engineered Natural Killer (CAR NK) Cells in Cancer Treatment; Recent Advances and Future Prospects. Elahi, R., Heidary, AH., Hadiloo, K., et al.[2022]

Genetically-engineered universal antigen presenting cells (uAPC) can significantly enhance the growth of both non-transduced and CAR-transduced natural killer (NK) cells, achieving over 900-fold expansion in just 2 weeks with high purity (over 99.9%).

NK cells expanded using uAPCs exhibit improved metabolic fitness and greater effectiveness against tumor cells, making them a promising option for adoptive CAR NK cell-based cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GMP-Compliant Universal Antigen Presenting Cells (uAPC) Promote the Metabolic Fitness and Antitumor Activity of Armored Cord Blood CAR-NK Cells. Liu, E., Ang, SOT., Kerbauy, L., et al.[2022]

Two methods for producing interleukin-15-activated NK cells were developed, yielding similar quantities of NK cells but with significantly lower T cell contamination in the NKIL15 product, enhancing its potential for clinical use.

Both NKIL15 and NKAE cell products demonstrated increased cytotoxic activity against cancer cells without harming healthy cells, and showed no genetic alterations, indicating their safety for therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How do we manufacture clinical-grade interleukin-15-stimulated natural killer cell products for cancer treatment? Fernández, L., Leivas, A., Valentín, J., et al.[2018]

Adoptive cell therapy, particularly using CAR T cells, has shown great promise in treating advanced cancers, but the need for patient-specific products limits its widespread use.

Natural killer (NK) cells offer a safer alternative as an allogeneic 'off-the-shelf' therapy, as they do not cause graft-versus-host disease (GVHD) and can be engineered with CARs to enhance their anti-tumor effects, making them a focus for future cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor Expressing Natural Killer Cells for the Immunotherapy of Cancer. Mehta, RS., Rezvani, K.[2019]

Natural Killer (NK) cells are crucial in fighting tumors and can be enhanced through immunotherapy, but traditional methods like IL-2 infusion can cause significant toxicity, limiting their use.

Innovative approaches like CAR-engineered NK cells offer a promising 'off-the-shelf' therapy option that avoids complications like graft-versus-host disease (GvHD) and can be sourced from unrelated donors, potentially improving cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploiting Human NK Cells in Tumor Therapy. Vacca, P., Pietra, G., Tumino, N., et al.[2020]

Genetic engineering of natural killer (NK) cells can enhance their tumor-killing ability and specificity, addressing limitations in their effectiveness in cancer immunotherapy.

Chimeric antigen receptor (CAR) NK cells, particularly those derived from human pluripotent stem cells, show promise in targeting both blood and solid tumors, providing a stable and expandable source for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The prospect of genetically engineering natural killer cells for cancer immunotherapy. Poon, AYC., Sugimura, R.[2022]

CAR-engineered natural killer (CAR-NK) cells show remarkable efficacy in cancer therapy and may offer advantages over traditional CAR-T cell therapies, particularly due to their ability to be used as 'off-the-shelf' products.

The review highlights the mechanisms of CAR-NK cells' anti-tumor activity and discusses ongoing challenges and clinical trials, suggesting that CAR-NK therapy holds significant promise for future cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor-engineered NK cells: new weapons of cancer immunotherapy with great potential. Wang, X., Yang, X., Yuan, X., et al.[2022]

References

1. France pubmed.ncbi.nlm.nih.gov

[Allogeneic CAR-NK cells: A promising alternative to autologous CAR-T cells - State of the art, sources of NK cells, limits and perspectives]. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor-Engineered Natural Killer (CAR NK) Cells in Cancer Treatment; Recent Advances and Future Prospects. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

GMP-Compliant Universal Antigen Presenting Cells (uAPC) Promote the Metabolic Fitness and Antitumor Activity of Armored Cord Blood CAR-NK Cells. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

How do we manufacture clinical-grade interleukin-15-stimulated natural killer cell products for cancer treatment? [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor Expressing Natural Killer Cells for the Immunotherapy of Cancer. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Exploiting Human NK Cells in Tumor Therapy. [2020]

8. England pubmed.ncbi.nlm.nih.gov

The prospect of genetically engineering natural killer cells for cancer immunotherapy. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor-engineered NK cells: new weapons of cancer immunotherapy with great potential. [2022]