Gamma Delta T cell Therapy - SunAct Cancer Institute

Therapies

What is Gamma Delta
T-cell Therapy?

Gamma delta T-cell therapy is an advanced form of immunotherapy that utilizes gamma delta (γδ) T-cells, a specialized sub-set of T-cells with the unique ability to target and destroy cancer cells.

How does Gamma Delta T-cell Therapy work?

Collection: T–cells are harvested from the healthy donor’s blood through a process known as leukapheresis.
Activation and Expansion: The collected gamma delta T–cells are then activated and expanded in a laboratory setting to increase their number and efficacy.
Infusion: The expanded gamma delta T–cells are infused back into the patient’s bloodstream.
Targeting Cancer: These cells directly recognize and kill cancer cells while also stimulating other immune cells to attack the tumor, enhancing the overall immune response.

Healthy Donor

Blood Sample

Mononuclear cells

High-purity γ δ T cells

Many cancer patients

Benefits

Broad Targeting: Capable of recognizing and attacking a wide spectrum of cancer cells.

Low Risk of Graft-Versus-Host Disease (GVHD): Reduced likelihood of GVHD compared to other T-cell therapies.

Potential for Combination Therapy: Can be combined with other treatments to potentially enhance therapeutic outcomes.

Tumor types and key ligands

Tumor type	Ligands Identified
Acute Lymphoblastic Leukemia	28-67% MICA/B 9-20% ULBP1-3
Acute myeloid leukemia	0-75% MICA/B 16-50% ULBP1 4-64% ULBP2 16-100% ULBP3
Bladder carcinoma	70% MICA
Brain cancer	90% MICA/B and ULBP1-3
Breast cancer	35-100% MICA/B, ULBP1-5
Cervical cancer	20% MICA, ULBP2
Chronic lymphatic leukemia	0-85% MICA/B 10-20% ULBP1-3
Chronic myeloid leukemia	28-80% MICA/B 12-20% ULBP1-3
Colorectal cancer	80-100% MICA/B ULBP1-5
Hepatocellular carcinoma	60-100% MICA

Tumor type	Ligands Identified
Lymphoma	20-44% MICA/B 12-20% ULBP1-3
Melanoma	50% MICA/B
Multiple myeloma	10-60% MICA 0-34% ULBP1-3
Neuroblastoma	86% MICA/B, ULBP1-3
Non-small-cell lung cancer	20-30% MICA/B, ULBP1-3
Ovarian carcinoma	50-97% MICA/B, ULBP1-5
Pancreatic cancer	68-89.3% MICA/B
Prostate cancer	75-95% MICA/B, sMICA/B
Renal carcinoma	>95% MICA/B
Sarcoma	100% MICA/B, ULBP1-3

Process

During Therapy

The infusion process is typically performed on an outpatient basis, but patients require close monitoring for potential adverse reactions.

After Therapy

Regular follow-up visits are crucial to monitor for side effects and evaluate treatment effectiveness.

Recovery

Side effects may include fatigue, fever, and other immune-related reactions.

How is it different from traditional treatment?

Gamma delta T–cells offer several unique features:

Recognition Mechanism: They target stress-induced molecules on cancer cells, allowing for broader targeting.
Reduced GVHD Risk: Lower incidence of GVHD compared to alpha beta T-cell therapies like CAR T.
Immune Functions: They exhibit both innate and adaptive immune characteristics, providing a versatile approach to treatment.

How effective is this treatment?

Clinical trials have shown that patients with advanced or recurrent cancers who undergo GDT therapy experience significant tumor shrinkage and prolonged survival. The therapy has particularly shown efficacy in cancers like Blood cancer and lung cancer.

Source: GD2 CAR T Cells Show Promise Against DMG - NCI

Who is eligible for Gamma Delta T-cell therapy?

GDT therapy is typically recommended for patients with advanced cancers who have not responded to conventional treatments like chemotherapy or immunotherapy. A thorough medical evaluation is required to determine eligibility.

Risks and side-effects

Cytokine Release Syndrome (CRS): May occur, leading to symptoms such as fever, fatigue, and low blood pressure.
Immune-Related Side Effects: Possible inflammation or autoimmune reactions.
Other Side Effects: May include infusion reactions, infections, and general fatigue.

Next steps if Gamma Delta T-cell Therapy doesn’t work

If Gamma delta T–cell therapy is not effective, alternative options may include

Other immunotherapies
Targeted therapies
Participation in additional clinical trials
Supportive care to manage symptoms and improve quality of life

Insurance Coverage

Insurance coverage varies by provider and plan. It is advisable for patients to consult with their healthcare provider and insurance company to understand coverage options and potential costs.