Weaponized Antibodies Use New Tricks to Fight Cancer

Excerpt:

“After decades of frustration, efforts to develop antibodies that can ferry drugs into cancer cells — and minimize damage to healthy tissue — are gathering steam. The next generation of these ‘weaponized antibody’ therapies, called antibody–drug conjugates (ADCs), is working its way through clinical trials.

“Researchers will gather to discuss this renaissance on 30 November at the Symposium on Molecular Targets and Cancer Therapeutics in Munich, Germany. The improvements come after the first wave of experimental ADCs failed to deliver on its promise.

” ‘Initially there was a lot of excitement, and then slowly many of them did not work,’ says Raffit Hassan, a cancer researcher at the US National Cancer Institute in Bethesda, Maryland. Now, he says, there are two new ADCs in phase III clinical trials, and many more in earlier-stage testing.”

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Novel Immune-Based Cancer Drug Imprime PGG Appears Effective in Certain Lung Cancer Patients

Adding the drug Imprime PGG to chemotherapy and antibody therapy may be effective for certain patients with non-small cell lung cancer (NSCLC). Imprime PGG contains a molecule called beta glucan, which can stimulate the body’s immune cells to destroy cancer cells. This process may be especially effective in patients with high levels of immune system proteins that bind to beta glucan, so-called antibeta glucan antibodies. In a recent clinical trial, patients with advanced NSCLC received the antibody drug cetuximab (Erbitux) and the chemotherapy agents carboplatin (Paraplatin) and paclitaxel (Taxol/Abraxane), and some were also given Imprime PGG. While survival across all patients was not affected by Imprime PGG treatment, it was increased in Imprime PGG-treated patients with high levels of antibeta glucan antibodies. Seventeen percent of these patients survived 3 years or more, while none of the other patient groups did.


Effect of New Lung Cancer Drug Depends on MET Protein Expression Levels

The cell protein MET is overexpressed in more than half of non-small cell lung cancer (NSCLC) tumors. MET overexpression is associated with worse prognoses and plays a role in drug resistance to EGFR inhibitors like erlotinib (Tarceva). A recent clinical trial examined the effects of onartuzumab, which inhibits MET function, on recurrent NSCLC. Patients received either onartuzumab and Tarceva or Tarceva only. In patients who overexpressed MET, adding onartuzumab increased the time until cancer progression and prolonged overall survival. In contrast, in patients without MET overexpression, adding onartuzumab worsened outcomes. This finding highlights the importance of diagnostic testing in choosing the best cancer treatment. A clinical trial investigating the onartuzumab-Tarceva combination in MET-overexpressing patients only is currently enrolling participants.


Antagonist Antibodies to PD-1 and B7-H1 (PD-L1) in the Treatment of Advanced Human Cancer—Letter


Antagonist Antibodies to PD-1 and B7-H1 (PD-L1) in the Treatment of Advanced Human Cancer—Letter


Clinical Laboratory in Indiana to Offer Blood Test for Lung Cancer

Mid America Clinical Laboratories, the largest clinical laboratory in Indiana, will begin offering EarlyCDT-Lung, a blood test designed to help diagnose lung cancer early on. EarlyCDT-Lung checks whether the patient has antibodies (immune system components) associated with a number of tumor-related proteins. High levels of such antibodies suggest that cancer may be present. EarlyCDT is highly accurate and specific for lung cancer, is less likely than computed tomography (CT) scans to falsely detect cancer when none is present, and can detect cancer-related antibodies up to 5 years before a tumor can be found using other screening methods. Such early detection is vital because lung cancer survival rates are higher when the disease is diagnosed at an early stage.


EGFR Antibody Increases Survival in Lung Cancer Trial

The new cancer drug necitumumab increased survival in the SQUIRE clinical trial, a phase III trial examining squamous non-small cell lung cancer (NSCLC).  Patients with stage IV squamous NSCLC who received necitumumab in addition to the chemotherapy agents cisplatin (Platinol) and gemcitabine (Gemzar) survived longer than those treated with chemotherapy alone. Necitumumab is an antibody (a type of immune system protein) that blocks the function of EGFR, a protein that plays an important role in the survival, spread, and blood supply of tumors.


Clinical Trial of New Drug to Treat Squamous Cell Lung Cancer Is Enrolling Patients

A clinical trial examining a new lung cancer drug is enrolling participants at numerous locations throughout the U.S. BMS-936558 (nivolumab) targets PD-1, a protein on the surface of immune cells that suppresses the immune response. By inhibiting PD-1, nivolumab ‘unleashes’ the immune system so it can continue its attack on tumors. The trial will investigate whether patients with advanced squamous cell carcinoma (SCC) of the lung, a type of non-small cell lung cancer (NSCLC), do better when treated with either nivolumab or the chemotherapy agent docetaxel (Taxotere). To find out more, call 855-216-0126 or visit the trial’s website.


New Drug May Mobilize the Immune System to Attack Tumors

A new drug called MPDL3280A appears to shrink tumors in patients with a range of different cancers, including lung cancer and melanoma. In an ongoing clinical trial, MPDL3280A shrank tumors in 21% of patients with advanced cancer. Response rates were even higher in subsets of patients with lung cancer (22%) or melanoma (29%). Treatment benefits lasted from 3 to 15 months and counting; 26 of the 29 patients who benefited continue to respond to this day. There was wide variation in how quickly patients responded to treatment, with some experiencing significant improvement within days, and others after weeks of unresponsiveness. MPDL3280A was generally well tolerated, with few cases of severe side effects.