cancer-therapy-and-biomarkers-2016

Volume 2, Issue 3(Suppl)

Oncol Cancer Case Rep

ISSN: 2471-8556 an open access journal

Page 28

Notes:

Cancer Therapy & Biomarkers 2016

December 05-07, 2016

conferenceseries

.com

CANCER THERAPY,

BIOMARKERS & CLINICAL RESEARCH

World Congress on

December 05-07, 2016 Philadelphia, USA

ImmTACs: Bi-specific TCR-based reagents for targeted cancer immunotherapy

Cheryl McAlpine

and

Bent Jakobsen

Immunocore Ltd, UK

mmune system based therapies constitute a promising class of treatment for many types of cancers. Whilst T cells can me-

diate tumor destruction, their effectiveness is limited due to negative thymic selection, down-regulation of HLA expression

by cancer cells and an immunosuppressive microenvironment. To overcome the poor immunogenicity of tumors, Immuno-

core has developed ImmTACs (immune mobilizing monoclonal T cell receptors (mTCR) against cancer). A soluble mTCR,

engineered to recognise a given tumor associated peptide-HLA complex with exceptionally high sensitivity and specificity,

redirects host polyclonal T cells via an anti-CD3 antibody fragment, facilitating targeted T cell recognition of tumors. Antigens

that exist on tumor cells but not on normal cells are rare, thus the selection and validation of appropriate target antigens and

the testing of ImmTACs for specificity is critical. Antigen candidates are selected based on their levels of expression in cancer

vs healthy tissues by RT-PCR and the presence of the targeted peptide on the cell surface is confirmed by mass spectrometry. As

ImmTACs are specific for humans, efficacy, specificity and off target effects are determined through a detailed molecular and

cellular testing programme, using antigen positive tumor cells and HLA appropriate primary human cell lines representing a

range of tissues. IMCgp100, the lead ImmTAC, is currently in a Phase I/II clinical trial for the treatment of advanced melano-

ma. The maximum tolerated dose has been established and emerging data demonstrate several durable responses. IMCgp100

is well tolerated and there is evidence of T cell mobilisation in the tumor microenvironment, release of cytokines and tumor

shrinkage.

Cheryl McAlpine et al., Oncol Cancer Case Rep 2016,2:3(Suppl)