TCR-T Cell Therapy for Cancer

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Christian S Hinrichs, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Christian Hinrichs

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Immunodeficiency, Severe autoimmune diseases, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment using modified immune cells to target specific cancers. It focuses on patients with certain metastatic cancers that produce an abnormal protein. The treatment aims to use the body's own enhanced immune system to fight cancer.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, participants on immunosuppressive drugs, including corticosteroids, are not eligible unless they meet specific criteria. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment KK-LC-1 TCR-T cell therapy for cancer?

Research shows that TCR gene-engineered T cells targeting the KK-LC-1 antigen can recognize and attack cancer cells in lab settings and reduce tumor size in mouse models. This suggests potential effectiveness in treating cancers that express the KK-LC-1 antigen, such as gastric and lung cancers. ^{1 2 3 4 5}

What safety data exists for KK-LC-1 TCR-T cell therapy in humans?

The research on KK-LC-1 TCR-T cell therapy shows that these engineered T cells can target cancer cells without affecting other human proteins, suggesting a level of safety in targeting specific cancer cells. However, detailed safety data in humans is not provided in the available studies. ^{1 2 4 5 6}

How is KK-LC-1 TCR-T cell therapy different from other cancer treatments?

KK-LC-1 TCR-T cell therapy is unique because it uses genetically engineered T cells to specifically target and attack cancer cells expressing the KK-LC-1 antigen, which is found in certain types of cancer like lung and gastric cancer. This approach is different from traditional treatments as it involves modifying the patient's immune cells to enhance their ability to recognize and destroy cancer cells, offering a more targeted and potentially effective treatment option. ^{3 4 5 7 8}

Research Team

Christian S Hinrichs, MD

Principal Investigator

Rutgers Cancer Institute of New Jersey

Eligibility Criteria

This trial is for adults over 18 with metastatic gastric, breast, cervical, or lung cancer that tests positive for KK-LC-1. They must have tried standard treatments without success and be in good physical condition (ECOG 0 or 1). Participants need functioning organs/marrow and no active infections like HIV or hepatitis. Pregnant women can't join, and those who can bear children must use contraception.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

It's been over 4 weeks since my last cancer treatment and any side effects are mild or stable.

I have up to 3 brain metastases treated with surgery or radiosurgery and stable for 1 month.

Exclusion Criteria

Not applicable.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Regimen

Participants receive a conditioning regimen consisting of cyclophosphamide and fludarabine

1 week

Treatment

Participants receive a single infusion of KK-LC-1 TCR-T cells followed by administration of aldesleukin

1 day

Initial Follow-up

Participants are monitored for adverse events and dose limiting toxicity to determine the maximum tolerated dose

4 weeks

Extended Follow-up

Participants are monitored for tumor response and duration of response

Up to 5 years

Treatment Details

Interventions

• Aldesleukin (Cytokine)
• KK-LC-1 TCR-T cells (CAR T-cell Therapy)

Trial Overview The trial is testing the safety and maximum dose of KK-LC-1 TCR-T cells combined with aldesleukin in treating certain cancers. It's a phase I study to see how patients tolerate this treatment and what their clinical response will be after receiving a conditioning regimen followed by the therapy.

Participant Groups

Group I: KK-LC-1 TCR-T cells Experimental Treatment 2 Interventions

Subjects will receive a conditioning regimen, KK-LC-1 TCR-T cells, and aldesleukin.

Who Is Running the Clinical Trial?

Christian Hinrichs

Lead Sponsor

Trials

3

Recruited

70+

Cancer Immunology and Metabolism Center of Excellence at Rutgers Cancer Institute of New Jersey

Collaborator

Trials

1

Recruited

30+

Iovance Biotherapeutics, Inc.

Industry Sponsor

Trials

26

Recruited

1,800+

T Cure Bioscience

Collaborator

Trials

1

Recruited

30+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

The study found that the tumor-associated antigen KK-LC-1 is expressed in 81.6% of gastric cancer specimens analyzed, indicating its potential role as a cancer/testis antigen (CTA) in this type of cancer.

KK-LC-1's high expression frequency compared to other CTAs suggests it could be a promising target for immunotherapy and diagnostic purposes in gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequent High Expression of Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) in Gastric Cancer. Shida, A., Futawatari, N., Fukuyama, T., et al.[2022]

The original monoclonal antibody Kmab34B3 successfully detected KK-LC-1 protein expression in 82% of gastric cancer tumor specimens, indicating its potential as a diagnostic tool for identifying cancerous cells.

Kmab34B3 also showed the ability to stain non-tumorous pyloric gland specimens, suggesting that it could be useful for detecting KK-LC-1 expression in both precancerous and cancerous stomach tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of Kita-Kyushu Lung Cancer Antigen-1 as Detected by a Novel Monoclonal Antibody in Gastric Cancer. Takahashi, Y., Fukuyama, T., Futawatari, N., et al.[2021]

Transducing γδT cells with a TCR specific to the KK-LC-1 lung cancer antigen demonstrated effective cytotoxic activity against lung cancer cells in vitro and inhibited tumor growth in vivo when administered shortly after cancer cell transplantation in mice.

The study found that TCRαβ-CD8 γδT cells were less effective against tumors that expressed FasL, suggesting that the interaction between FasL on cancer cells and Fas on TCRαβ-CD8 γδT cells may induce apoptosis, limiting the therapy's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of adoptive immunotherapy with KK-LC-1-specific TCR-transduced γδT cells against lung cancer cells. Ichiki, Y., Shigematsu, Y., Baba, T., et al.[2023]

A novel T cell receptor (TCR) targeting the Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) has been developed, showing effective recognition and regression of tumors expressing this antigen in preclinical models, particularly in epithelial cancers like gastric cancer.

The KK-LC-1 TCR-Ts demonstrated specificity for cancer cells without cross-reactivity to other human proteins, suggesting a potentially safe therapeutic option for treating epithelial malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer targeting by TCR gene-engineered T cells directed against Kita-Kyushu Lung Cancer Antigen-1. Marcinkowski, B., Stevanović, S., Helman, SR., et al.[2021]

KK-LC-1 is overexpressed in hepatocellular carcinoma (HCC) tissues and its high levels are associated with poor survival outcomes, indicating its potential as a prognostic biomarker.

The study reveals that KK-LC-1 promotes HCC progression by enhancing cell growth, migration, and invasion through a novel signaling pathway involving presenilin-1 and the Notch1/Hes1 pathway, driven by hypomethylation of CpG islands.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypomethylation-mediated activation of cancer/testis antigen KK-LC-1 facilitates hepatocellular carcinoma progression through activating the Notch1/Hes1 signalling. Chen, Z., Zuo, X., Pu, L., et al.[2021]

A new monoclonal antibody (clone 34B3) was developed to detect the protein expression of KK-LC-1, a cancer/testis antigen, in breast cancer samples, showing a significant difference in detection rates compared to gene expression (11.8% for gene vs. 52.9% for protein).

KK-LC-1 protein expression was found in all cases of triple-negative breast cancer (n=8) and in all tumors lacking estrogen receptor expression, suggesting its potential as a target for immunotherapy in these aggressive breast cancer subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of KK-LC-1 Protein, a Cancer/Testis Antigen, in Patients with Breast Cancer. Kondo, Y., Fukuyama, T., Yamamura, R., et al.[2021]

The study successfully transduced TCRαβ genes into γδ T cells, enabling them to specifically target and kill lung cancer cells expressing the KK-LC-1 antigen, demonstrating effective cytotoxic activity in both laboratory assays and in a mouse model.

Adoptive transfer of these genetically modified γδ T cells significantly suppressed the growth of tumors in mice, indicating that this approach could be a promising new strategy for adoptive immunotherapy in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of human γδ T cells transducted with CD8 and with T-cell receptors of tumor-specific cytotoxic T lymphocytes. Hanagiri, T., Shigematsu, Y., Kuroda, K., et al.[2021]

Natural killer (NK) cells play a crucial role in the immune response against lung cancer, but their effectiveness can be hindered by factors such as ineffective activation and tumor-specific challenges, which limits the success of current immunotherapies.

Combining strategies to reactivate NK cells with other treatments may improve clinical outcomes for lung cancer patients, addressing the limitations of existing therapies and enhancing anti-tumor immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NK cell-based therapeutics for lung cancer. Pockley, AG., Vaupel, P., Multhoff, G.[2020]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Frequent High Expression of Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) in Gastric Cancer. [2022]

2. Greece pubmed.ncbi.nlm.nih.gov

Expression of Kita-Kyushu Lung Cancer Antigen-1 as Detected by a Novel Monoclonal Antibody in Gastric Cancer. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Development of adoptive immunotherapy with KK-LC-1-specific TCR-transduced γδT cells against lung cancer cells. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Cancer targeting by TCR gene-engineered T cells directed against Kita-Kyushu Lung Cancer Antigen-1. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Hypomethylation-mediated activation of cancer/testis antigen KK-LC-1 facilitates hepatocellular carcinoma progression through activating the Notch1/Hes1 signalling. [2021]

6. Greece pubmed.ncbi.nlm.nih.gov

Detection of KK-LC-1 Protein, a Cancer/Testis Antigen, in Patients with Breast Cancer. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Antitumor activity of human γδ T cells transducted with CD8 and with T-cell receptors of tumor-specific cytotoxic T lymphocytes. [2021]

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

NK cell-based therapeutics for lung cancer. [2020]