medwireNews: A neoantigen-targeting personalized cancer vaccine (PCV) has shown promising antitumor activity in people with high-risk, fully resected renal cell carcinoma (RCC).
After more than 3 years from treatment, none of the nine participants of the phase 1 trial had experienced recurrence, report Toni Choueiri (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) and co-authors in Nature.
They additionally highlight that “the PCVs (with or without locally delivered ipilimumab) were substantially less toxic than adjuvant immune checkpoint inhibition.”
The team continues: “The favourable toxicity profile of PCVs highlights the potential beneficial role for these neoantigen-targeting vaccines in RCC, either as monotherapy or in combination with immune checkpoint inhibition.”
Giving the background to the study, the researchers explain that “[n]eoantigens are derived from tumour-specific mutations and represent important targets of T cell-mediated antitumour immunity.”
They add that “PCVs directed at neoantigens have the potential to steer antitumour immune responses towards cancer-cell-specific epitopes,” but for tumors with a low mutational burden, such as RCC, “PCVs have faced implementation challenges in both initial manufacturing and in the effective generation of vaccine-specific immune responses.”
In light of “the existing signal for immunotherapy efficacy and ongoing unmet clinical need of RCC,” Choueiri and colleagues investigated a novel peptide-based PCV in nine patients with stage III (n=7) or IV (n=2) clear cell disease who underwent curative intent surgery.
PCVs were successfully generated and administered after surgery for all the patients, five of whom additionally received subcutaneous ipilimumab at a dose of 2.5 mg adjacent to the vaccine site.
Each PCV comprised four pools of up to five synthetic long peptides targeting neoantigens, admixed with 0.5 mg of the vaccine adjuvant poly-ICLC per pool, explain the study authors, adding that “[t]he vaccine was administered on days 1, 4, 8, 15 and 22 for vaccine priming and then on weeks 12 and 20 for the booster phase.”
At a median follow-up of 40.2 months from surgery and 34.7 months from vaccination initiation, none of the participants experienced recurrence and the median disease-free survival time was unreached.
“One patient died from mental-health-related complications unrelated to RCC or to treatment,” but this patient had no evidence of disease at the last follow-up, notes the team.
All the patients experienced injection-site reactions and eight had flu-like symptoms, but there were no toxicities of grade 3 or more in the cohort.
Furthermore, analysis of immune activity showed that “the vaccine antigens were immunogenic in all patients, typically against multiple epitopes, which led to polyfunctional memory T cell responses,” write the researchers.
“Vaccination rapidly and durably expanded T cell clonotypes, with expansion persisting years after the last vaccine dose. Moreover, in most patients, the PCV resulted in immune reactivity against autologous tumour cells.”
Choueiri et al say that “[t]hese observations, in conjunction with the absence of recurrence in all nine vaccinated patients, highlights the promise of PCVs as effective adjuvant therapy in RCC.”
But they conclude: “Although the initial immunological activity and clinical results of our small phase I study are encouraging, additional larger-scale studies will be required to confirm these finding[s] and to fully understand the potential clinical efficacy of this approach.”
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