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.
http://www.onclive.com/publications/oncology-live/2016/vol-17-no-7/tils-advancing-as-melanoma-immunotherapy-option/2
[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 works....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
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 works....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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