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

Abstract

We conducted a systematic review and meta-analysis of randomized control trials to formally assess the safety and efficacy of autologous whole cell vaccines as immunotherapies for solid tumors. Our primary safety outcome was number, and grade of adverse events. Our primary efficacy outcome was clinical responses. Secondary outcomes included survival metrics and correlative immune assays. We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for studies published between 1946 and August 2020 using any autologous whole cell product in the treatment of any solid tumor. The Cochrane Randomized Controlled Trial risk of bias tool was used to assess risk of bias. Eighteen manuscripts were identified with a total of 714 patients enrolled in control and 808 in vaccine arms. In 698 patients receiving at least one dose of vaccine, treatment was well tolerated with a total of 5 grade III or higher adverse events. Clinical response was reported in a minority (n = 2, 14%) of studies. Autologous cell vaccines were associated with improved overall (HR 1.28, 95% CI 1.01–1.63) and disease-free survival (HR 1.33, 95% CI 1.05–1.67) over thirteen and ten trials respectively. Where reported, immune assays correlated well with clinical outcomes. Our results suggest that autologous whole cell vaccination is safe and efficacious in increasing survival in patients undergoing treatment for solid tumors.Registration: PROSPERO CRD42019140187.

Targeted immunotherapy for glioblastoma involving whole tumor-derived autologous cells in the upfront setting after craniotomy

“…Along with greater understanding of the underlying immunology of the various immunotherapies has come increasing evidence of clinical benefit, including evidence of the benefit of cancer vaccines. Despite being one of the first immunotherapies to be attempted [ 9 ], therapeutic cancer vaccines including short and long peptides [ 10 ], DNA [ 11 , 12 ], RNA [ 13 ], and autologous tumor-derived cells [ 14 ] are conspicuously absent from the therapeutic arsenal [ 3 ]. This is likely because, as opposed to successful prophylactic treatments [ 15 ], therapeutic cancer vaccines must induce an immune response to existing cancer cells that have survived prior therapies [ 16 ].…”

“…They most often utilize sizable amounts of resected tumor material, rather than small biopsies, avoiding exclusion of relevant antigens due to tumor heterogeneity or sampling error. They do not require prediction of linear peptide antigens and include post-translationally modified antigens, which can be important drivers of tumor growth but are not encoded in mutations and therefore are not covered by neoantigen-based approaches [ 14 , 18 – 20 ]. Additionally, they can include innate immune stimuli, although these can be balanced by immunosuppressive tumor cell components if there is no limit to the release of tumor cell contents [ 21 , 22 ].…”

“…Additionally, they can include innate immune stimuli, although these can be balanced by immunosuppressive tumor cell components if there is no limit to the release of tumor cell contents [ 21 , 22 ]. Several clinical trials reporting evidence of efficacy for autologous tumor-based cancer vaccines have recently been conducted [ 14 , 23 ]. We used PubMed to search for the terms “glioblastoma,” “newly diagnosed,” “vaccine,” and “immunotherapy” to search for relevant articles reporting phase 2 or 3 trials for review.…”

“…The BDCs are then implanted in patients’ abdominal wall between the rectus sheath and muscle inferolateral to the umbilicus (the lymphatic watershed below possible immunosuppressive GBM-tolerized draining lymph nodes) for approximately 48 h [ 40 ]. As opposed to other autologous cancer vaccine modalities, which require multiple dosages over weeks and months [ 14 , 41 ], IGV-001 consists of only one treatment given within 48 h of craniotomy within a standard of care hospitalization.…”

A Therapeutic Vaccine Targeting Rat BORIS (CTCFL) for the Treatment of Rat Breast Cancer Tumors

“…This has led various groups to test the efficacy of vaccines targeting whole tumor cells, different tumor-associated antigens (TAAs) [ 7 , 8 , 9 ] including cancer-testis (CT), antigens [ 10 ] and, given the association of tumor mutational burden and ICI efficacy, more recently, neoantigens [ 11 , 12 , 13 ], in animal models and clinical trials. These various anti-tumor vaccines have had mixed and generally modest success in terms of clinical response rates [ 13 , 14 ]. It should be mentioned that tumor-associated self-tolerance can limit the usage of many TAAs and some CT-antigens [ 15 ].…”