Science History About Me

Oncology    Immunology

Cancer kills without discrimination to wealth, gender, age, nor ethnicity. However, while rates are increasing primarily due to longevity increases and environmental factors, great strides have been made in the understanding and treatment of this horrible disease. As I've studied, I have gained insights that give me hope that we will soon be winning the battle.

Adoptive Cell Therapy; Chimeric Antigen Receptors

Imagine a person with Stage IV Chronic Lymphocytic Leukemia, a cancer of the white blood cells. A scan of his bone marrow shows almost complete replacement of healthy cells with cancerous. The cancer is chemorefractory, meaning it survives every dose even while his normal rapidly dividing cells do not. Now, instead of the normal treatment progression and a poor prognosis, some healthy T cells are extracted from his blood. They are processed, induced to replicate, and then the large resulting colony of cells is infused back into his blood. Thirty days later, a scan reveals his bone marrow to be clear of the cancer and another 6 months later shows the same; a complete resolution to the cancer.

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Chimeric Antigen Receptor: Target erbB2

The process of tuning cytotoxic T lymphocytes (CTL) to kill cancer cells is undoubtedly a spectacular innovation but it can be precarious. The primary function of a CTL is to bind and kill any cell found bearing the ligand of the CTL’s antigen receptor (the CAR in this case) on its membrane. There are many factors that must be addressed when tailoring the therapy to treat a given pathology; the most significant of which is selecting the CAR’s ligand (its target). Other factors include how many CAR+ T cells should be injected and how to control their proliferation and longevity after injection. After completing the reading that went into this post I am not certain that, one, erbB-2 is a suitable CAR target, and two, I have been convinced that the use of chemotherapy as a neoadjuvant (administered just prior) to any targeted molecular therapy should be questioned.

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Intracellular Caspase-Modulating Chimeric Antigen Receptor

In this review, a targeted cancer therapeutic is proposed providing direct targeting of tumor-specific or -associated antigens from within malignant cells: (i) with an antibody-based biological agent; (ii) utilizing a constitutively active apoptosis effector that is inhibited or nonfunctional until the antibody binds its agonist. Two possible configurations to achieve this end are provided. One embeds an scFv control into the apoptosis-inducing effector using an intein and the second employs a zinc-finger-based targeting and activating mechanism based on an approach known as sequence-enabled reassembly of proteins. Although the latter might provide a broader range of targets, because zinc fingers bind directly to DNA rather than transcribed protein, this review focuses on the former owing to the large body of clinical data available..

Available through ScienceDirect