IGV-001 Cellular Immunotherapy for Newly Diagnosed Glioblastoma: Overcoming the Logistic Challenge

Eric T Wong ^1,2* Deus Cielo ^1,2 Konstantina Svokos ^1,2 Curt Doberstein ^1,2 Prakash Sampath ^1,2 John E Donahue ^1,2 Michael Punsoni ^1,2 Nuno Rodrigues ¹ Francesca Rothell ¹ Robert Edwards ¹ Elaina Wang ^1,2 Tori Riccelli ^1,2 Carlin Chuck ^1,2 Elias A Shaaya ^1,2 Rahul Sastry ^1,2 Rohaid Ali ^1,2 Belinda Shao ^1,2 Hael Abdulrazeq ^1,2 Felicia W Sun ^1,2 Joshua Feler ^1,2 Santos E Santos Fontánez ^1,2 Natalie Amaral Nieves ^1,2 Cody Dobertsein ^1,2 Jennifer Dailey ^1,2 Christine Yu ^1,2 Sasmit Sarangi ^1,2 Heinrich Elinzano ^1,2 Jerrold L Boxerman ^1,2 Esther Yu ^1,2 Howard Safran ^1,2 Attila A Seyhan ³ Wafik El- Deiry ^1,2 Sharonda Keith ¹ Ziya L Gokaslan ^1,2 Clark C Chen ^1,2 Athar Malik ^1,2

• ¹ Rhode Island Hospital, Providence, Rhode Island, United States
• ² Warren Alpert Medical School, Brown University, Providence, Rhode Island, United States
• ³ Brown University, Providence, Rhode Island, United States

Background: IGV-001 is a type of cellular immunotherapy currently being investigated for treating glioblastoma (NCT04485949). It uses the patient's tumor to elicit an autologous immune response.Methods: The process involves (i) craniotomy for maximum safe resection of the glioblastoma, (ii) ex-vivo treatment of the tumor with an anti-sense oligonucleotide against insulin-like growth factor 1 receptor followed by irradiation, (ii) placement of the treated tumor in multiple biodiffusion chambers, which are implanted into the patient's abdominal sheath to elicit an immune response, and (iii) explantation of the chambers 48 hours later. The clinical trial was open at 32 sites in the United States, and eligible subjects were randomized in a 2:1 ratio to receive biodiffusion chambers containing either conditioned glioblastoma tissue or a placebo. Patients subsequently proceeded to standard-of-care treatment with concomitant radiation-temozolomide, followed by 6 cycles of adjuvant temozolomide.Results: The execution of the IGV-001 protocol procedure is complicated and involves a multistep process requiring mobilization of multiple services within the cancer center of a tertiary care hospital, including neurosurgery, neuro-oncology, radiation oncology, neuroradiology, cancer clinical trial office, and operating room personnel to fulfill the pre-specified protocol requirements in a timely fashion.Conclusions: We have learned a great deal in the process of developing and executing our internal procedures for this clinical trial. Our description of the IGV-001 protocol workflow may serve as a "blueprint" for future implementation of this type of cellular immunotherapy at other centers. We further discuss some of the lessons we have learned during the trial.