Feasibility of T-cell-based adoptive immunotherapy in the first 12 patients with advanced urothelial urinary bladder cancer. Preliminary data on a new immunologic treatment based on the sentinel node concept.
BACKGROUND
Expected 2-yr survival for patients with urothelial urinary bladder cancer (UBC) with lymph node involvement (pN2) is 20%, regardless of standard neoadjuvant/adjuvant oncologic treatment. Tumor-reactive lymphocytes are present in sentinel nodes (SNs) draining human bladder cancer and display immunologic function on restimulation in vitro. Metinel nodes (MNs) drain secondarily from metastatic tumors and also possess tumor-reactive lymphocytes, which might be a source for adoptive T-cell immunotherapy.


OBJECTIVE
To determine if MN detection and subsequent expansion of autologous T-helper cells with subsequent reinfusion was feasible and safe to perform in patients with metastatic UBC.


METHODS
In an open trial, the first 12 included patients are described. Patients were prospectively selected from a single tertiary academic center and had metastatic UBC. All 12 patients were preoperatively staged as T2-T4b N1-2 and/or M0-M1 or MX.


METHODS
MNs were excised in conjunction with intended cystectomy. T lymphocytes were extracted with enhancement and expansion of tumor specific T-helper cells, followed by reinfusion of expanded T cells.


METHODS
All patients were preoperatively staged with transurethral resection of the bladder and routine computed tomography scan. Intended detection of MNs was performed intraoperatively with intended cystectomy. Harvested T cells were evaluated and cell cultures were established. Assessment of reinfusion of expanded, autologous, tumor-specific T-helper cells to six of the patients was performed, focusing on adverse effects.


CONCLUSIONS
In six patients, it was feasible to administer the treatment. Reinfusion of these T cells was performed without any major adverse effects. In six other patients, we encountered technical failures.


CONCLUSIONS
A novel adoptive immunotherapy based on T cells from tumor-draining lymph nodes is feasible in advanced UBC. Infusion of expanded, autologous, tumor-specific T-helper cells might be a future treatment option in metastasized UBC. Long-term overall survival remains to be determined.
Sherif
Amir
A
Department of Urology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden. amir.sherif-abdel-hadi@karolinska.se
Hasan
Mudhar N
MN
Marits
Per
P
Karlsson
Mona
M
Winqvist
Ola
O
Thörn
Magnus
M
D000368:Aged; D000938:Antigen-Presenting Cells / Q000276:immunology; D002295:Carcinoma, Transitional Cell / Q000556:secondary / Q000628:therapy*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007376:Interleukin-2 / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D009367:Neoplasm Staging; D010865:Pilot Projects; D011446:Prospective Studies; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000637:transplantation*; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000628:therapy*
D007376:Interleukin-2