Background \& Rationale: For years, most tumor immunotherapy researches have focused on T cell and natural killer (NK) cell therapies, most of which involve amplification and modification of the patient's immune cells for reinfusion therapy. However, for the treatment of solid tumors, there is currently little breakthrough. Recently, researchers have reported a colony of cancer-resistant mice developed from a single mouse that was immune to multiple lethal cancer cell injections. Further research revealed that such anti-cancer immunity can cause rapid shrinkage or disappearance of the tumors in other cancer-bearing mice. Interestingly, this therapeutic effect is due to the donor granulocytes, instead of T cells or NK cells. Infusion of granulocytes is a classic therapy in treating infection associated with granulocytopenia. Currently, clinical collection of blood components, including isolation of granulocytes, is a mature technique. The infusion of granulocytes is a viable anticancer therapy combining the classic technique and novel anticancer approach. This proposed trial will test whether granulocyte infusions from healthy unrelated donors can be used to treat advanced cancer. In the proposed trial, up to 100 Subjects with advanced cancer can be entered. Each patient will be given a dose of (2.0-5.0)x10\^10 granulocytes from a different healthy donor every week over a course of 5 doses. The trial will evaluate the subject's cancer 7, 30, 90 and 180 days after the last infusion.
Granulocyte anti-cancer therapy refers to a method in which healthy donor granulocytes with high cancer-killing activity are collected and infused into a specific cancer patient by matching, to achieve the therapeutic anticancer effect. In this proposed trial, up to 100 Subjects with advanced cancer can be entered. Potentially hundreds of healthy Donor-participants will be recruited. First, granulocyte donors will be identified via in-vitro assay of Cancer Killing Activity (CKA), which screens healthy Donor-participants for those with anticancer activity of more than 80%. Secondly, after donor-recipient blood matching, (2.0-5.0)x10\^10 granulocytes will be collected from each donor, accounting for about 1/10 of the human body. Each patient will be given a dose of (2.0-5.0)x10\^10 granulocytes from a different donor per week over a course of 5 doses (with an ideal total infusion of 2X10\^11 granulocytes). After each infusion, the patients will be monitored carefully for possible adverse events. If adverse events occur, the infusion can be slowed down or stopped until the adverse events can be managed. The trial will observe the subject's cancer 7, 30, 90 and 180 days after the last infusion. Target lesions, non-target lesions, and new lesions will be evaluated via medical imaging and tumor markers. The responses will be compared against the measurements at baseline.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
100
Granulocytes cross-matched for ABO-Rh and CMV; bioactivity of anti-cancer ability meets the criteria.
Department of Oncology, Shanghai East Hospital
Shanghai, Shanghai Municipality, China
RECRUITINGProgression free survival (PFS)
The trial will observe the subject's progression free survival for 3 months after the granulocyte infusions are completed.
Time frame: 90 days post treatment
median Overall Survival (mOS)
The patients will be followed 1 week, 1 month, 3 months and 6 months after the last treatment. Median Overall Survival will be measured as the length of time from the date of inclusion that half of the patients are still alive.
Time frame: 180 days post treatment
Objective Response Rate (ORR )
Objective Response Rate will be evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. If a response is achieved in a patient, the evaluation will be repeated 4-6 weeks after the first evaluation to confirm the response.
Time frame: 180 days post treatment
Disease Control Rate (DCR)
Disease Control Rate will be measured as the percentage of patients achieved complete response (CR), partial response (PR) and stable disease (SD) to the treatment (evaluated based on RECIST 1.1).
Time frame: 180 days post treatment
Quality of life measured in ECOG
ECOG Scale of Performance Status will be evaluated for patients after treatment to reflect impact on quality of life.
Time frame: 180 days post treatment
Treatment-related adverse events
Incidence of treatment-related adverse events as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
Time frame: 5 weeks of treatment and 1 month post treatment
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