14 Participants Needed

Genetically Engineered Lymphocytes for Melanoma

Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Loyola University
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

Do I need to stop taking my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications, but it does exclude patients taking steroids for disease control or pain management. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Genetically Engineered Lymphocytes for Melanoma?

Research shows that genetically engineered T cells can effectively target and reduce melanoma tumors. Studies have demonstrated that these engineered cells can expand and maintain their ability to fight cancer, leading to significant tumor regression in patients with melanoma.12345

What safety data exists for genetically engineered lymphocytes used in cancer treatment?

Genetically engineered T cell therapies, like CAR-T cells, have shown promise in treating cancer but come with safety concerns such as cytokine release syndrome (a severe immune reaction), neurotoxicity (nerve damage), and potential off-target effects (unintended impacts on healthy cells). Efforts are being made to improve safety, including integrating safety switches to manage these risks.16789

How does the treatment with genetically engineered lymphocytes for melanoma differ from other treatments?

This treatment is unique because it uses genetically engineered lymphocytes (a type of white blood cell) to target melanoma cells specifically, by modifying them to express highly reactive T-cell receptors (TCRs) that recognize melanoma antigens. This approach aims to enhance the body's immune response against cancer cells, which is different from traditional treatments that may not specifically target cancer cells in this way.12101112

What is the purpose of this trial?

This is a phase one trial to determine if genetically engineered lymphocytes can be safely delivered to patients with metastatic melanoma.

Research Team

MN

Michael Nishimura, PhD

Principal Investigator

Loyola University Chicago

Eligibility Criteria

Adults with metastatic melanoma that can be measured, who are in good physical condition (ECOG PS 0 or 1), and have specific genetic markers (HLA-A2 positive, tyrosinase positive). They must not be pregnant, have had certain treatments recently, or suffer from severe systemic diseases. Prior immunotherapies are allowed except for Tyrosinase immunotherapy.

Inclusion Criteria

I know my cancer's BRAF status and have either failed or refused Vemurafenib therapy.
My melanoma has spread and can be measured by tests or exams.
It has been over 3 months since my last anti-CTLA-4 antibody treatment.
See 6 more

Exclusion Criteria

My melanoma's BRAF V600E mutation status is unknown, or I am responding to or haven't been offered Vemurafenib.
Patients must not be pregnant or nursing because of the potentially harmful effects of these agents on a developing fetus. Women/men of reproductive potential must have agreed to use an effective contraceptive method.
I have not had active brain melanoma or treatment for it in the last 6 months.
See 13 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy Preparative Regimen

Participants undergo a non-myeloablative and lymphodepleting chemotherapy preparative regimen

1-2 weeks

Treatment

Participants receive genetically engineered lymphocytes with low dose IL-2

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • Dose 1
  • Dose 2
  • Dose 3
  • Dose 4
Trial Overview This phase one trial is testing the safety of different doses of genetically engineered lymphocytes to treat patients with advanced melanoma. The study will progressively test four increasing dose levels to find a safe dosage.
Participant Groups
4Treatment groups
Experimental Treatment
Group I: Dose 4Experimental Treatment1 Intervention
Subjects will then receive a single infusion of autologous bulk TIL 1383I TCR transduced T cells supported with low dose IL-2. Autologous bulk TIL 1383I TCR transduced T cells means the infusion will consist of a polyclonal mixture of CD4+ and CD8+ T cells expressing the TIL 1383I TCR. Subjects in cohort 4 will receive 7.5 x 107 TIL 1383I TCR transduced T cells per kg body weight.
Group II: Dose 3Experimental Treatment1 Intervention
Subjects in cohort 3 will receive 2.5 x 107 TIL 1383I TCR transduced T cells per kg body weight.
Group III: Dose 2Experimental Treatment1 Intervention
cohort 2 will receive 7.5 x 106 TIL 1383I TCR transduced T cells per kg body weight.
Group IV: Dose 1Experimental Treatment1 Intervention
Subjects in cohort 1 will receive 2.5 x 106 TIL 1383I TCR transduced T cells per kg body weight

Find a Clinic Near You

Who Is Running the Clinical Trial?

Loyola University

Lead Sponsor

Trials
161
Recruited
31,400+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Findings from Research

Engineered cells for costimulatory enhancement (ECCE) significantly accelerated the expansion of tumor-infiltrating lymphocytes (TIL) from melanoma biopsies, increasing TIL numbers and improving their antitumor reactivity (P=0.001).
ECCE also enhanced TIL generation from nonmelanoma-cell suspensions, suggesting that this method could broaden access to TIL therapy for patients who are currently ineligible for treatment.
Augmented lymphocyte expansion from solid tumors with engineered cells for costimulatory enhancement.Friedman, KM., Devillier, LE., Feldman, SA., et al.[2023]
Engineered T cells with an affinity-enhanced T-cell receptor (TCR) against MAGE-A3 led to severe cardiogenic shock and death in two patients, indicating serious and unpredictable off-target effects despite preclinical safety assessments.
Autopsy results showed significant heart damage and T-cell infiltration, but no MAGE-A3 expression was found in heart tissues, suggesting that the T cells may have targeted an unrelated peptide from a muscle protein, highlighting the need for better specificity testing in TCR engineering.
Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma.Linette, GP., Stadtmauer, EA., Maus, MV., et al.[2023]
Adoptive transfer of tumor-reactive lymphocytes has shown success in treating metastatic melanoma, leading to the development of T cell receptor (TCR) gene engineering to enhance normal T cells' ability to target tumors.
Initial clinical studies indicate that TCR gene-engineered T cells can effectively mediate tumor regression in patients, showcasing the potential of this approach for treating melanoma and other cancers.
Genetic engineering with T cell receptors.Zhang, L., Morgan, RA.[2023]

References

Engineering hematopoietic stem cells to create melanoma specific CTL. [2021]
Augmented lymphocyte expansion from solid tumors with engineered cells for costimulatory enhancement. [2023]
Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma. [2023]
White paper on adoptive cell therapy for cancer with tumor-infiltrating lymphocytes: a report of the CTEP subcommittee on adoptive cell therapy. [2020]
Genetic engineering with T cell receptors. [2023]
Cas9-induced targeted integration of large DNA payloads in primary human T cells via homology-mediated end-joining DNA repair. [2023]
Improving the efficacy and safety of engineered T cell therapy for cancer. [2020]
Nonclinical safety assessment of engineered T cell therapies. [2022]
Engineering Hematopoietic Cells for Cancer Immunotherapy: Strategies to Address Safety and Toxicity Concerns. [2018]
10.United Statespubmed.ncbi.nlm.nih.gov
Immunotherapy of metastatic melanoma using genetically engineered GD2-specific T cells. [2022]
11.United Statespubmed.ncbi.nlm.nih.gov
Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. [2023]
12.United Statespubmed.ncbi.nlm.nih.gov
Gene therapy with autologous, interleukin 2-secreting tumor cells in patients with malignant melanoma. [2018]
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