Review ArticleReview

Personalized immunotherapy in cancer precision medicine

Kazuma Kiyotani, Yujiro Toyoshima and Yusuke Nakamura
Cancer Biology & Medicine November 2021, 18 (4) 955-965; DOI: https://doi.org/10.20892/j.issn.2095-3941.2021.0032

Article Figures & Data

Figures

  • Figure 1
    Figure 1

    Summary of frequency of actionability and patients’ response rates in genomic profiling-based clinical trials. Approximately 40% of the patients had potentially actionable mutations/alterations, but only 10%–15% were treated with genotype-guided appropriate drugs.

  • Figure 2
    Figure 2

    Workflow of neoantigen prediction pipeline from genome sequencing data. The first step is HLA class I genotyping (at 2-field level) based on WES data. The second and third steps are somatic variant call and detection of mutant RNA expression. Non-synonymous SNVs and indels, which alter amino acid sequences, were selected and further analyzed. The last step is binding affinity prediction of mutated peptides to individuals’ HLA molecules. WES, whole-exome sequencing; RNAseq, RNA sequencing; SNVs, single nucleotide variations; Indels, insertions/deletions.

Tables

  • Table 1

    Selected clinical trials of genotype-based therapy

    InstituteYearSample sizePlatformTissue samplePatients with actionable mutationsPatients enrolled in genotype-matched trialsORR of patients matched to treatment based on genotype
    MD Anderson Cancer Center520152,00011–50 gene panelsFFPE789/2,000 (39.5%)83/2,000 (4.2%)Not available
    Memorial Sloan Kettering Cancer Center2201612,670341 or 410 gene panelsFFPE3,792/10,336 (36.7%)527/5,009 (10.5%)Not available
    Dana-Farber/Harvard Cancer Center620163,727275 gene panelsFFPE31/50 (62.0%)16/50 (32.0%)Not available
    Princess Margaret Cancer Centre420161,64023–48 gene panelsFFPE25%84/1,640 (5.1%)19%
    Gustave Roussy8820171,03530–75 gene panels + aCGHFF411/1,035 (39.7%)199/1,035 (19.2%)11%
    University of Michigan892017556WGS, WES, RNAseqFFNot available3%–11%Not available
    Lyon9020192,57969 gene panels + aCGHFFPE699/2,579 (27.1%)182/2,579 (7.1%)13%

    aCGH, array conparative genomic hybridization; WGS, whole-genome sequencing; WES, whole-exome sequencing; FFPE, formalin-fixed paraffin-embedded; FF, fresh-frozen; ORR, objective response rate.

    • Table 2

      Published clinical trials of personalized neoantigen vaccines

      InstituteYearCancer typeVaccine typePatient numberClinical responseOther clinical response information
      CRPRSDPD
      Washington University School of Medicine912015MelanomaDendritic cell vaccine31020–
      BioNTech772017MelanomaRNA vaccine13–––58 recurrent-free 12–23 months2 CR, 1 PR, 1 SD for relapses in combination with ICIs
      Dana-Farber/Harvard Cancer Center782017MelanomaLong peptide vaccine + Poly-ICLC6–––24 recurrent-free 20–32 months2 CR for relapses in combination with ICIs
      Dana-Farber/Harvard Cancer Center792019GlioblastomaLong peptide vaccine + Poly-ICLC80008PFS 7.6 months, OS 16.8 months
      Immatics Biotechnologies, BioNTech802019GlioblastomaLong/short peptide vaccine + Poly-ICLC + GM-CSF1502211PFS 14.2 months, OS 29.0 months
      Dana-Farber/Harvard Cancer Center, BioNTech812020MelanomaLong peptide vaccine + Poly-ICLC2711574PFS 23.5 months
      NSCLC180792PFS 8.5 months
      Bladder cancer151392PFS 5.8 months

      NSCLC, non-small cell lung cancer; Poly-ICLC, polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose; GM-CSF, granulocyte macrophage colony-stimulating factor; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; PFS, progression-free survival; OS, overall survival; ICIs, immune checkpoint inhibitors.

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