Cancer Program Annual Report - Eisenhower Medical Center

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E I S E N H O W E R M E D I C A L C E N T E R antigens of tumor cells, and present the above antigens to T cells and other immune regulatory cells via uploading dose antigens on the major histocompatibility molecule (MHC). In the second phase, the T cells would need to receive a co-stimulatory signal from APC cells via interaction of the CD 28 on the T cells surface with B7.1 molecules on the APC cells. Once the co-stimulatory signal has arrived, the T cells are activated and ready to attack the tumor cells and destroy them. However, prior to this activation, the tumor cells actually turn off the T cell invasion by expressing inhibitory molecules and signals called inhibitory checkpoints via expression of the inhibitory molecule CTLA-4 on surface of the T cells that are competing for CD 28 molecules, or expression of PD-L1 (Programmed Cell Death Ligand-1) or PD-L2 on the tumor cells, which would then react with T cells PD-1 receptors. To block the effect of these inhibitory molecules on T cells, and in order to keep T cells activated, there has been a variety of antibodies produced in the lab against CTLA-4 or PD-L1 or PD-L2 and PD-1. (See Figure 1 and Figure 2.) The antibody against CTLA-4, Ipilumamb, has already been used for treatment of metastatic melanoma. There is also variety of antibodies against PD-1 or PD-L1 in clinical trials with different efficacy or toxicity profile. (See Figure 3 on page 10.) The response rate of these compounds in preliminary trials is nearly 30 percent with at minimum progression free survival or stable disease of six months or more. They are well-tolerated treatments and have different toxicity profile and efficacy. They have shown activity both against adenocarcinoma and squamous cell carcinomas. For example, the first of the PD-1 blocking agents have shown a lot of activity against squamous cell cancer but not as much against adenocarcinoma. Moreover, the other molecules, such as, MPDL3280A has shown activity against both adenocarcinoma and squamous cell carcinoma. They can cause pulmonary toxicity (pneumonitis). Among all of the compounds, MPDL3280A has the least pneumonitis A B © 2012 American Association for Cancer Research Figure 1, Figure 2 9
E I S E N H O W E R M E D I C A L C E N T E R Differences Between Immune Checkpoint Inhibitors PD-1 Nivolumab IgG4 fully human MK-3475 IgG4 engineered humanized CT-011 IgG4 humanized PD-L1 MPDL3280A IgG1 engineered fully human BMS-936559 IgG4 fully human MEDI4756 IgG4 engineered fully human Figure 3 effect with a very good efficacy profile so far. These compounds are in phase II trials either alone or in combination with chemotherapy or other targeted treatments such as EGFR pathway inhibitors and even in combination treatment with radiation therapy for stage III disease. They also have promising activity against other solid tumors. It is anticipated the above immunotherapies will soon become part of standard treatments. Immune Checkpoint Blockade: Beyond PD-1/PD-L1 Figure 4 In the future, we will combine these antibodies with a host of other antibodies to either block the inhibitory pathways or use them with antibodies which would stimulate immune system activity. For a list of novel agents at work see Figure 4. Eisenhower Medical Center: A Leader in Lung Cancer Screening United States Preventive Services Task Force (USPSTF) Recommends Lung Cancer Screening Stephanie Farrell, MBA, CPHQ, CCRC Coordinator, Clinical Cancer Research On July 29, 2013, the United States Preventive Services Task Force (USPSTF) recommended annual lowdose computed tomographic (CT) lung screening for high-risk individuals. This recommendation is significant because of possible future screening coverage by Medicare, Medicaid and private insurers — encouraging news for those who are insured and at high risk for developing lung cancer. Without screening and intervention, individuals who develop lung cancer have only a 15 percent five-year survival rate. The USPSTF based its recommendation on research published in 2012 by the National Lung Screening Trial (NLST), and a newly created clinical practice 10
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