Central PA Medicine Spring 2018 - 7

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treatment options despite advances in
early detection and the large number of
anticancer medications on the market.
Scientists believed that they could rectify this by approaching cancer therapy
from a novel perspective-reawakening
and harnessing the power of a patient's
immune system to combat this disease.
This led to the development of chimeric
antigen receptor (CAR) T cell therapy.
CARs, which are synthetic receptors
that combine the targeted-specificity of
antibodies with the effector capabilities
of T cells, have emerged as a promising
anticancer therapy. Upon binding to a
cancer cell with their antibody component,
CARs become activated and turn on
downstream signaling pathways within
the T cell which ultimately result in
cytotoxic killing and release of cytokines
to upregulate the immune response. 4
Demonstrating efficacy in animal studies,
CAR T cell therapy was approved for
clinical trials where a patient's T cells were respiratory distress, and fever, arises due and primary mediastinal B cell lymphoma
harnessed, reactivated and expanded in to the profound release of cytokines upon patients, demonstrated significantly less
vivo with antibody-coated beads, trans- CAR activation.7 Neurological changes side effects and better complete response
duced with a viral vector containing the can present as aphasias, seizures, delirium, rates compared to the current FDA-apCAR, further expanded and reinfused and global encephalopathy. 7 Protocols proved products. 12 Juno will apply for
back into the patient after conditional are in place to manage these conditions FDA approval before the end of 2018.11
chemotherapy.5 In 2010, scientists at the should they arise. Although the exact
National Cancer Institute were the first to cause of these toxicities has yet to be
Since CAR T therapy is a one-time
report successful regression of advanced defined, researchers have speculated that treatment, pharmaceutical companies
lymphoma in one patient undergoing it may be due to semi-random insertional will be charging a premium to recoup
CAR T cell therapy.6 In 2011, researchers mutagenesis leading to ununiform CAR development costs with limited coverage
from Memorial Sloan Kettering Cancer expression when using a retroviral vector by insurance companies at the moment.
Center (MSKCC) were the first to show during the initial T cell transduction. 9 Currently, Novartis charges $475,000,
complete remission in 8 relapsed or When researchers at MSKCC used a gene while Gilead's therapy costs $373,000.11
refractory B-cell Acute Lymphoblastic targeting approach for transduction, they Despite these steep hurdles, the promiLeukemia (ALL) patients in a Phase I observed enhanced T cell potency with nence and utility of CAR T cell therapy
clinical trial. 7 In 2012, the Children's minimal side effects in mouse models.10 will only continue to grow as the clinical
Hospital of Philadelphia demonstrated They hope that similar results will be portfolio expands beyond hematological
similar promising results for pediatric observed in patients in clinical trials.
malignancies as more cancer targets are
relapsed B-cell ALL after they treated
discovered. Clinical trials are opening
Emily Whitehead with CAR T cell therapy
In 2017, the promise of CAR T cell worldwide for such pathologies as gliomas,
achieving complete remission.8
therapy became a reality when Novartis's glioblastomas, sarcomas, neuroblastoma,
Kymriah and Kite's Yescarta received mesotheliomas, pancreatic, breast, and
Although CARs have demonstrated FDA approval for the treatment of pe- liver cancers, giving terminal patients
clinical efficacy in hematological malig- diatric relapsed/refractory B-cell ALL hope. 13 CAR T cell therapy is here to
nancies, they have the potential to elicit and Diffuse Large B cell lymphoma, stay, and will soon become an additional
two main complications- Cytokine respectively.11 Juno Therapeutics' Liso-cel,
Release Syndrome (CRS) and neurological indicated for use in Diffuse Large B cell,
Continued on page 8
changes. CRS, defined by hypotension, Non-Hodgkin's, follicular, mantle cell,
Central PA Medicine Spring 2018 7
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