Cancer Clinical Trial
Official title:
Adoptive Cell Therapy Across Cancer Diagnoses
This study will perform tumor-infiltrating lymphocyte (TIL)-based adoptive T-cell therapy in combination with checkpoint inhibition on cancer patients across all cancer diagnoses.
Adoptive cell therapy (ACT) is a personalized form of immunotherapy, where lymphocytes
isolated from the patient's own tumor tissue are expanded 1000-fold ex-vivo and then infused
back into the patient. The lymphocytes are then able to recognize and attack remaining cancer
cells. This approach has shown remarkable clinical results in several trials conducted
worldwide for patients with advanced melanoma - some with durable remissions. Promising
clinical results were obtained in smaller trials where patients with disparate solid tumors
were treated with tumor-infiltrating lymphocytes (TILs). At Center for Cancer Immune Therapy
(CCIT) at Herlev Hospital, there are currently clinical trials undergoing in ovarian and
renal cancer, and internationally ACT is being tested in an increasing number of cancer
diagnoses, some trials are even recruiting patients across cancer types. Studies have shown
that a high intratumoral infiltration with TILs in is correlated to the general clinical
outcome of the disease in virtually all solid tumors, and thus clinical trials with TIL-based
ACT to different cancer diagnoses have been undertaken.
To support the TIL-mediated tumor elimination, in classical ACT protocols patients go through
a highly specialized treatment regime before and after TIL infusion. This regime includes
lymphodepletion with 7 days non-myeloablative chemotherapy, to provide an immunological
window of opportunity for the infused TILs, and concomitant immune stimulation with
interleukin-2 (IL-2). Checkpoint inhibition to support the anti-tumor activity of TILs is
currently under extensive investigation in several other trials worldwide. Thus,
lymphodepletion and IL-2 stimulation are well-established as supportive therapy and already
an integrated part of current ACT protocols and while checkpoint inhibition is a new addition
at CCIT; internationally other centers have ongoing comparable trials.
Drug-based immunotherapy in the form of checkpoint inhibitors (anti-PD-1 and anti-CTLA-4) has
yielded impressive clinical results across tumor histologies. Recent results indicate that
the effect of immunotherapy relies not so much on the cancer diagnoses but rather on the
genomic and immunologic features of the individual patient's cancer disease. Both ACT and
checkpoint inhibition work by tipping the immunological balance in favor of activation and
away from suppression or avoidance by the cancer cells. Scientific evidence now show that
administering anti-CTLA-4 and PD-1 could provide a benefit in the ACT setting, and several
ongoing clinical trials are testing combinations of ACT and checkpoint inhibition. To
synergistically maximize the immunological potential, we wish to combine ACT with an
anti-CTLA-4 antibody (Ipilimumab) prior to tumor resection and an anti-PD-1 antibody
(Nivolumab) in combination with TIL infusion.
Patients will be treated with one dose of Ipilimumab 14 days before undergoing surgery to
harvest tumor material for TIL production. Patients is admitted on day -8 in order to undergo
lymphodepleting chemotherapy with cyclophosphamide and fludara starting day -7. On day -2
patients will start treatment with Nivolumab every 2 weeks for a total of 4 doses to increase
the activity of the infused TIL product.
Available evidence indicates that ACT is a safe and feasible treatment option in an
increasing number of solid tumors, and that it should be tested in all cancer patients
regardless of their cancer diagnosis.
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