TAA-T Cell Therapy for Solid Cancers

Recruiting at 1 trial location

Overseen By Fahmida Hoq, MBBS

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Children's National Research Institute

Must not be taking: Immunosuppressants, Chemotherapy

Disqualifiers: HIV, Pregnancy, Allogeneic transplant, others

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

Compensation: Varies

Number of Visits: 2

Duration: 45 days

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TAA-T cell therapy (tumor-associated antigen-specific T cell therapy) to determine its safety for individuals with difficult-to-treat solid tumors. These tumors have either returned, not responded well to previous treatments, or still show signs after treatment. The trial seeks participants with specific types of solid tumors, such as Ewing sarcoma or osteosarcoma, who have undergone conventional treatments like chemotherapy or surgery. Participants will be grouped by age to test different doses and methods of TAA-T therapy. Those dealing with these cancers and treatments might consider this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering a chance to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have taken systemic steroids within 1 week of the TAA-T infusion and certain immunosuppressive medications within 28 days. If you are receiving lymphodepleting chemotherapy, you should not have taken chemotherapy or immunomodulatory medications within the last 2 weeks before treatment.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that T cell therapy, which targets cancer cells, is considered safe based on current data. In earlier studies, patients who received similar treatments generally tolerated them well. While some side effects may occur, they are usually manageable. This treatment uses the body's own immune cells to locate and attack cancer cells. As this is an early phase trial, the main goal is to determine the treatment's safety.

If the treatment proves safe in this phase, it indicates that any side effects are not severe or can be controlled. This is encouraging for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about TAA-T cell therapy for solid cancers because it offers a unique approach by harnessing the body's own immune system. Unlike traditional treatments like chemotherapy or radiation that target cancer cells directly, TAA-T cell therapy uses specially engineered T cells that are programmed to recognize and attack tumor-associated antigens on cancer cells. This targeted mechanism could potentially lead to fewer side effects and more precise cancer cell elimination. Additionally, the personalized nature of TAA-T cells may improve treatment effectiveness across different cancer types, providing hope for patients who may not respond well to existing treatments.

What evidence suggests that TAA-T cell therapy might be an effective treatment for solid cancers?

Research shows that a new treatment called TAA-T therapy could be promising for treating solid cancers. In this trial, researchers will administer TAA-T therapy to participants in two separate arms based on age groups. Earlier studies have tested this therapy for its ability to fight tumors, including breast cancer, and suggest it is potentially safe. TAA-T therapy targets specific proteins on cancer cells, helping the immune system attack the tumor more effectively. Initial results from these studies are positive, with some patients experiencing tumor shrinkage. While more research is needed, TAA-T therapy is seen as a hopeful new option for people with difficult-to-treat cancers. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for patients with high-risk solid tumors like Ewing sarcoma or neuroblastoma, who have not responded well to standard treatments. Participants must be in stable condition without recent steroid use or infections and agree to contraception if applicable. They should match at least one HLA allele with the TAA-T therapy and meet specific health criteria such as adequate organ function.

Inclusion Criteria

My blood tests show enough neutrophils and platelets while on chemotherapy.

My liver enzymes are within a normal range for my age.

Pulse oximetry of >90% on room air

Exclusion Criteria

I haven't received specific immune system treatments in the last 28 days.

I had a stem cell transplant using my own cells within the last 60 days.

Pregnant or lactating females

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TAA-T therapy with dose escalation to determine safety and anti-tumor activity

45 days

1 visit (in-person) for each infusion

Follow-up

Participants are monitored for safety and effectiveness after TAA-T infusion

45 days

1 visit (in-person) at day 45

Extension

Additional dose of TAA-T may be administered if criteria are met

Minimum of 45 days apart from the first dose

What Are the Treatments Tested in This Trial?

Interventions

• Tumor-associated antigen-specific T cell (TAA-T)

Trial Overview

The study tests a new cancer treatment using T cells that target tumor-associated antigens (TAA-T). It's for those whose tumors express certain antigens and haven't improved after conventional therapies. The trial will gradually increase doses to find the safest amount of TAA-T cells that can be given.

How Is the Trial Designed?

Group I: Arm B for patients age ≥6 years and <18 years Experimental Treatment 1 Intervention

Arm B will enroll patients age ≥6 years and \<18 years. TAA-T product will first be administered to patients as monotherapy at dose level 1 to determine safety. Following demonstration of safety in dose level 1, lymphodepleting chemotherapy will be administered prior to the first dose of TAA-Ts on the dose escalation phase (dose levels 2 and 3). The TAA-T product will be assessed for safety and anti-tumor activity.

Group II: Arm A for patients age ≥18 years and <70 years Experimental Treatment 1 Intervention

Arm A will enroll patients age ≥18 years and \<70 years. TAA-T product will first be administered to patients as monotherapy at dose level 1 to determine safety. Following demonstration of safety in dose level 1, lymphodepleting chemotherapy will be administered prior to the first dose of TAA-Ts on the dose escalation phase (dose levels 2 and 3). The TAA-T product will be assessed for safety and anti-tumor activity.

Who Is Running the Clinical Trial?

Children's National Research Institute

Lead Sponsor

Trials

227

Recruited

258,000+

Published Research Related to This Trial

Naturally occurring T cells that target tumor-associated antigens (TAAs) are frequently found in cancer patients, indicating that tumors may have some level of immunogenicity.

The review highlights that while certain TAAs elicit strong T cell responses, others do not, suggesting that understanding these differences is key to developing effective T cell-directed immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural T cell immunity against cancer. Nagorsen, D., Scheibenbogen, C., Marincola, FM., et al.[2022]

Adoptive T-cell therapy using tumor-infiltrating lymphocytes (TILs) has shown significant promise in treating metastatic melanoma, leading to the development of genetically engineered T cells that can specifically target tumor-associated antigens (TAAs).

Initial clinical studies indicate that these genetically engineered T cells, including those with tumor antigen-specific T cell receptors (TCRs) and chimeric antigen receptors (CARs), can effectively cause tumor regression, although safety concerns, particularly regarding potential 'on-target, off-organ' toxicity, must be carefully managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving the efficacy and safety of engineered T cell therapy for cancer. Shi, H., Liu, L., Wang, Z.[2020]

Tumor-associated antigen-specific cytotoxic T lymphocytes (TAA-CTL) were safely generated and infused into patients with multiple myeloma and non-Hodgkin lymphoma, with no significant adverse reactions reported during the treatment.

In a small group of 7 patients, TAA-CTL therapy showed promising efficacy, as 5 patients experienced positive clinical effects, and an increase in specific immune responses was observed 2-3 weeks post-infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Research of Dendritic Cell-Mediated Tumor-Associated Antigen-Specific Cytotoxic T Lymphocytes in the Treatment of Multiple Myeloma and Non-Hodgkin Lymphoma]. Li, XH., Xue, L., Xu, H., et al.[2020]

Human T cells can be genetically modified to express tumor-associated antigens, making them potential candidates for effective antigen-presenting cells in cancer immunotherapy.

The successful induction of tumor-specific T cell immune responses requires the activation of T cells using CD3/CD28 antibodies along with proinflammatory cytokines like IL-7 and IL-12, highlighting the importance of these components in developing cellular cancer vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modification of T lymphocytes to express tumor antigens. Foster, AE., Song, XT.[2021]

In a first-in-human trial involving 15 patients with relapsed or refractory solid tumors, tumor-associated antigen cytotoxic T cells (TAA-Ts) were administered safely without any dose-limiting toxicities, demonstrating a promising new therapeutic approach.

Of the evaluable patients, 73% showed stable disease or better at day 45 post-infusion, with 6 patients remaining progression-free for a median of 13.9 months, indicating that TAA-Ts can effectively stabilize disease and prolong time to progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy of Relapsed and Refractory Solid Tumors With Ex Vivo Expanded Multi-Tumor Associated Antigen Specific Cytotoxic T Lymphocytes: A Phase I Study. Hont, AB., Cruz, CR., Ulrey, R., et al.[2020]

Engineered T cells expressing T-cell receptors (TCRs) can specifically target tumor-associated antigens (TAAs), making them a promising approach in cancer treatment, particularly for hematologic malignancies.

Current early-phase clinical trials are testing TCR-T therapies targeting three different TAAs, while preclinical studies are exploring many more, indicating a broad potential for safe and effective cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-Cell Receptor-Based Immunotherapy for Hematologic Malignancies. Biernacki, MA., Brault, M., Bleakley, M.[2023]

There is growing interest in therapeutic vaccination as a cancer treatment, moving beyond early vaccines that used whole tumor cells or fragments, which had limited success.

Current research is focused on developing next-generation cancer vaccines that target specific tumor-associated antigens (TAAs), with ongoing efforts to identify and deliver these antigens effectively for better therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-associated antigens: from discovery to immunity. Lewis, JD., Reilly, BD., Bright, RK.[2022]

Adoptive T-cell therapy (ACT) has shown the ability to induce complete and lasting tumor regression in certain cancers, particularly metastatic melanoma, with some patients potentially being cured.

Recent advancements in identifying mutated gene products as targets for TILs and the use of engineered T cells (like those expressing chimeric antigen receptors) suggest that ACT could be expanded to treat a wider range of malignancies beyond melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploiting the curative potential of adoptive T-cell therapy for cancer. Hinrichs, CS., Rosenberg, SA.[2023]

Recombinant monoclonal antibodies (MAbs) are becoming important in cancer therapy, especially when used alongside traditional anti-cancer drugs, enhancing treatment effectiveness.

Combining antibody therapy with toxins or radioisotopes, and developing immune cells like cytotoxic T-lymphocytes (CTLs) or natural killer (NK) cells that target tumor-associated antigens (TAAs), could significantly improve cancer immunotherapy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible applications of antibodies or their genes in cancer therapy. Kuroki, M., Huang, J., Shibaguchi, H., et al.[2007]

In a first-in-human trial involving 10 heavily pre-treated patients with relapsed or metastatic breast cancer, multi-antigen-targeted T cells (multiTAA-T) were well tolerated with no treatment-related toxicities, indicating a promising safety profile for this therapy.

One patient experienced prolonged disease stabilization for 5 months, which was linked to the in vivo expansion and persistence of T cells targeting specific tumor antigens, along with evidence of broader immune activation against non-targeted tumor antigens in 7 out of 10 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer. Hoyos, V., Vasileiou, S., Kuvalekar, M., et al.[2022]

Adoptive cellular therapy, particularly using tumor-infiltrating lymphocytes (TILs), shows significant promise in treating cancers like melanoma, indicating a need for further development in clinical settings.

Genetically engineered T cells can enhance antitumor activity, but there are risks of toxicity when these cells target normal tissues, highlighting the need for careful balance in future therapies and clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of adoptive cell therapy for cancer: a clinical perspective. Hawkins, RE., Gilham, DE., Debets, R., et al.[2021]

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