Safety and efficacy of autologous whole cell vaccines in hematologic malignancies: A systematic review and meta‐analysis

Abstract

Autologous cell vaccines use a patient's tumor cells to stimulate a broad antitumor response in vivo. This approach shows promise for treating hematologic cancers in early phase clinical trials, but overall safety and efficacy remain poorly described. We conducted a systematic review assessing the use of autologous cell vaccination in treating hematologic cancers. Primary outcomes of interest were safety and clinical response, with secondary outcomes including survival, relapse rate, correlative immune assays and health‐quality related metrics. We performed a search of MEDLINE, Embase and the Cochrane Register of Controlled Trials including any interventional trial employing an autologous, whole cell product in any hematologic malignancy. Risk of bias was assessed using a modified Institute of Health Economics tool. Across 20 single arm studies, only 341 of 592 enrolled participants received one or more vaccinations. Primary reasons for not receiving vaccination included rapid disease progression/death and manufacturing challenges. Overall, few high‐grade adverse events were observed. One death was reported and attributed to a GM‐CSF producing allogeneic cell line co‐administered with the autologous vaccine. Of 58 evaluable patients, the complete response rate was 21.0% [95% CI, 10.4%‐37.8%)] and overall response rate was 35.8% (95% CI, 24.4%–49.0%). Of 97 evaluable patients for survival, the 5‐years overall survival rate was 64.9% (95% CI, 52.6%–77.2%) and disease‐free survival was 59.7% (95% CI, 47.7%–71.7%). We conclude that, in hematologic malignancies, based on limited available data, autologous cell vaccines are safe and display a trend towards efficacy but that challenges exist in vaccine manufacture and administration.

Safety and efficacy of autologous cell vaccines in solid tumors: a systematic review and meta-analysis of randomized control trials

“…www.nature.com/scientificreports/ Of the 808 enrolled patients, 698 received at least one dose of vaccine representing a successful vaccination rate of 86%. This rate is significantly better than what was observed in our systematic review of autologous whole cell vaccination in hematologic malignancies (58%) but still suggests that the ability to manufacture vaccines represents a barrier in the context of solid tumors 12 . In the current study, the main reason for patients not receiving vaccination was withdrawal or being lost to follow-up followed by post-operative complications / death and patients becoming ineligible 18,20,36,[46][47][48] .…”

“…In the current study, the main reason for patients not receiving vaccination was withdrawal or being lost to follow-up followed by post-operative complications / death and patients becoming ineligible 18,20,36,[46][47][48] . Unlike our systematic review of autologous whole cell vaccination in hematologic malignancies manufacturing challenges represented a reason for which only a minority of patients were not vaccinated 12 .…”

“…Clinical responses included complete response (CR) and overall response (OR). In our published protocol, clinical response was primarily intended to be applied to our companion study of autologous cell vaccination hematologic malignancies where CR and OR could be reported in the context of minimal residual disease 6 , 12 . We nevertheless recorded and reported on this outcome where it was reported in studies investigating solid tumors.…”

Application of Nanotechnology in Therapeutic Cancer Vaccines

“…Compared with other immunotherapies targeting specific antigens, it retains the relatively intact tumor antigens of the patient and avoids the immune escape of tumor cells. [ 39 ] Allogeneic tumor cell vaccines are prepared from specific types of tumor cells rather than specific patient tumor cells. They also present several advantages, including ease of access, mass production, and storage.…”

Clinical significance of anticancer vaccines (literature review)

“…Пухлинні клітини під впливом фізичних факторів (швидке заморожування/ відтаювання, тепловий шок, опромінення тощо) втрачають здатність проліферувати, або проводять їх лізис з утворенням лізатів пухлин. Під час аналізу 173 опублікованих досліджень, в яких брали участь понад 3000 хворих, які отримували вакцини на основі пухлинних клітин або лізатів пухлини, об'єктивна відповідь на терапію зафіксована у 8,1 % проти 3,6 % хворих, яким проводилася антиген-специфічна терапія [4]. Однак у клінічних випробуваннях більшість вакцин не продемонстрували значної терапевтичної ефективності та не сприяли виробленню стійкого адаптивного протипухлинного імунітету.…”