Oncology

Immuno-Oncology

Harnessing the Body’s Immune System

The growing understanding of tumor cells’ ability to evade immune surveillance has led to advances in the field of immune-oncology.¹" the following:

Malignant cells manipulate a variety of physiological mechanisms involved in antigenicity, immune activation, T-cell priming and recruitment, and upregulation of checkpoint molecules.1 Many of these mechanisms may be impacted simultaneously to promote tumor cell survival.1 Immunotherapies harness the body’s own immune system to fight cancer by using different immunological pathways to enhance antitumor responses.^1,2

GSK is exploring different clinical assets aimed at augmenting the immune response, reducing immune suppression, and modulating the tumor microenvironment.^3,4

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Synthetic Lethality

Accumulation of DNA damage and genomic instability are pervasive characteristics of human tumors and are caused by defects in DNA repair.^1,2 Deficiencies in essential DNA damage repair in cancer cells may increase dependency on an alternate repair pathway for cell survival.² Synthetically lethal therapies aim to combine pharmacologic inhibition of these alternate repair pathways with inherent defects in DNA damage repair to selectively kill tumor cells while sparing healthy tissue.^2-4 GSK is investigating a clinical asset that utilizes the power of synthetically lethal interactions to fight malignant cells in a variety of cancers.

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Cancer Epigenetics

Aberrant gene expression, regulated in large part by epigenetic mechanisms, is a hallmark of cancer.¹ “Epigenetics” refers to heritable changes in gene expression that arise from changes in chromosomes without altering the DNA sequence.² DNA methylation and posttranslational modifications of histones play key roles in regulating gene expression.^1,3 Deregulation of these epigenetic mechanisms can lead to aberrant expression of oncogenes and tumor suppressors in cancer cells that can enhance proliferative signals, impair cell death, promote angiogenesis, and facilitate metastasis. GSK is investigating compounds that work by altering these epigenetic pathways.

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Cell Therapy

The physiologic role of central and peripheral tolerance mechanisms is to limit unchecked immune responses that can lead to autoimmunity.¹ In cancer, these mechanisms are major limitations to effective T-cell mediated antitumor immunity.¹ Oncology cell therapy uses adoptive transfer of engineered T cells that may mediate antitumor effects. In adoptive cell therapy, T cells are isolated from the patient, engineered to present an enhanced TCR that recognizes a specific antigen, and then reintroduced into the patient.^1,2 This innovative approach generates T cells that may be more efficient at targeting cancer cells and may overcome the barriers of tolerance mechanisms² GSK is developing an engineered TCR T-cell clinical asset designed to target a tumor-specific antigen and eliminate malignant cells in solid tumors and hematologic malignancies.

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Cell Therapy - Coming Soon