Adoptive Immunotherapy for Liver Cancer

Survival after T cell receptor-redirected autologous T cell therapy against relapsed hepatitis B virus-induced hepatocellular carcinoma in a liver transplanted patient.

Status

Completed

Phases

Early Phase 1

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12616000129482

Acronym

Nil

Enrollment

Registered

2016-02-04

Start date

2016-01-05

Completion date

2016-01-05

Last updated

2020-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

This protocol describes the production of autologous, ex vivo-activated, Hepatitis B Virus (HBV) envelope gene specific, T cell receptor (TCR) redirected-T lymphocytes for re-infusion into a patient with HBV-induced hepatocellular carcinoma (HCC) that has relapsed following liver transplantation. Using current protocols, this patient can now only be offered palliative therapy. An immunological therapy based on adoptive transfer of HBV-specific T cells targeting HBV expressing HCC cells can potentially kill tumor cells while sparing normal tissue. The ability of T cells to specifically recognize cancer cells expressing specific antigens has been the basis of immunlogical therapies with TCR-modified T cells that have been successful in malignancies such as B cell lymphoma (N Engl J Med 2011;365:725-733) and melanoma (Science 2015;348:62-68). Here we propose to treat a patient with a relapse of HBV-induced HCC with T cells that have been engineered to express an envelope gene-specific TCR. These TCR-redirected T cells should exclusively recognize the HCC but not normal liver hepatocytes. .

Interventions

8 infusions at 7 day intervals of increasing doses of 10,000 (1 infusion), 100,000 (1 infusion), 1,000,000 (1 infusion) and 5,000,000 (5 infusions) cells /kg of autologous t cell receptor-redirected T cells that recognise a hepatitis B virus envelope peptide (FLGPLLVLQA) presented by HLA-Cw*0801. The cells will be prepared in the New Zealand Liver Transplant Research laboratory at Auckland City Hospital and administered by IV infusion by nursing staff.

Study design

Allocation

Non-randomised trial

Intervention model

Single group

Primary purpose

Treatment

Masking

Open (masking not used)

Eligibility

Sex/Gender

All

Age

21 Years to No maximum

Healthy volunteers

Inclusion criteria

Relapsed post-transplant hepatocellular carcinoma

Exclusion criteria

Significant psychiatric disease.

Outcome results