Saturday, April 16, 2016

TILs (tumor infiltrating lymphocytes) - advancing as melanoma immunotherapy and new trial

After nearly 30 years of research, tumor-infiltrating lymphocyte technologies are being investigated as a means of producing personalized immunotherapy for patients with metastatic melanoma in a small clinical trial that may help open the door for broader application in other solid tumor types.

[In an interview] Weber said acute toxicities that have been associated with TIL therapy include hemorrhagic cystitis, cytoxan-induced syndrome of inappropriate antidiuretic hormone, neutropenic fever/ sepsis, and hypotension/capillary leak. He said researchers have adjusted to these toxicities by limiting IL-2 to 6 doses after TIL infusion therapy. Chronic toxicities have included fatigue, neuropathy, vitiligo, and uveitis.

One key challenge in TIL therapy that has been partially overcome, Weber said, is finding a better way to grow TILs. The process used to take 6 or more hours, multiple incubators, and multiple technicians. Today, he said, with the use of bioreactors and a closed system, the process is more efficient and only requires one technician. There is still more work to be done to make the process even better, he noted. The approach is moving forward in the phase II, multicenter LN-144 study, which aims to assess the safety, feasibility, and antitumor activity of this treatment followed by IL-2 for patients with metastatic melanoma who are refractory to at least one systemic therapy.3 Researchers are seeking to enroll 20 patients.

For trial inclusion, patients must have measurable disease with at least one lesion that is resectable for TIL generation; that is, at least 1.5 cm in diameter and able to be removed with minimal morbidity. Exclusion criteria include prior cell transfer therapy that included a nonmyeloablative or myeloablative chemotherapy regimen, more than three brain metastases, and current use of a systemic steroid regimen.

This trial is an exciting early step, according to Steven A. Fischkoff, MD, chief medical officer of Lion Biotechnologies, Inc, a New York City–based company that is developing the TIL therapy under an orphan drug designation. He said that focusing on TILs is a forward-looking approach to immunotherapy. Weber, who is a member of Lion’s scientific advisory board, said the technology holds promise for a variety of tumor types. Besides melanoma, other cancer types that might prove amenable to TIL therapy include renal cell carcinoma, ovarian cancer, glioblastoma multiforme, lung cancer, and cervical cancer, he said.

“You can definitely grow TILs from a variety of tumors,” Weber said. “In the old days, people tried to do it and couldn’t figure out what to do. It turns out to be much easier to do than we thought.”

TIL therapy is tough.  I've lost some dear to me after they tried it.  On the other hand...when it is amazing.  It makes sense.  It holds promise.  Not sure how benign and dependable it has really become....that's what the amazing ratties who sign up for this trial will show us.  Fingers crossed for everyone. -c

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