Immunogenicity Profiles of Selected Gene Therapies


Strategies are being considered to avoid triggering a host immune response to gene therapies. These include1,2:

Voretigene neparvovec-rzyl3

  • Viral vector: AAV

  • Transgene: RPE65

  • Delivery method: In vivo – subretinal injection to the eye

  • Target site: Retina

  • Immunogenicity in clinical trials

    • Immune reactions were mild
    • No patients experienced a clinically significant cytotoxic T-cell response to the AAV vector or transgene
    • Patients received systemic corticosteroids pre- and post-treatment, which may have reduced the potential of an immune response

*Brand name: Luxturna™. AAV, adeno-associated virus; RPE65, retinal pigment epithelium-specific 65 kDa protein.


  • Viral vector: Lentiviral

  • Transgene: Chimeric antigen receptor (CAR)

  • Delivery method: Ex vivo

  • Target site: T cells

  • Immunogenicity in clinical trials

    • Cytokine release syndrome* occurred in 79% of the 68 pediatric and young adults with r/r ALL and 74%of the 106 adult patients with r/r DLBCL
      • Median time to onset was 3 days
      • Median time to resolution was 8 days
      • Five patients died within 30 days of treatment
      • Severe or life-threatening CRS should be treated using tocilizumab with/without corticosteroids
    • Pre-existing and treatment-induced anti-murine CAR19 antibodies did not affect the clinical response, initial expansion, and persistence

*CRS is a disorder characterized by fever, tachypnea, headache, tachycardia, hypotension, rash, and/or hypoxia caused by the release of cytokines5. ALL, acute lymphoblastic leukemia; CRS, cytokine release syndrome; DLBCL, diffuse large B-cell lymphoma; r/r, relapsed or refractory.


  1. Kay MA. Nat Rev Genet 2011;12(5):316–328.
  2. Sack BK, Herzog RW. Curr Opin Mol Ther 2009;11(5):493–503.
  3. LuxturnaTM [package insert]. Philadelphia, PA; Spark Therapeutics, Inc.; 2017. Available at: Accessed July 24, 2019.
  4. Kymriah® [package insert]. East Hanover, NJ; Novartis Pharmaceuticals Corporation; 2018. Available at: Accessed July 24, 2019.
  5. U.S. Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, 2017. Available at: Accessed April 4, 2019.
  1. Nayak S, Herzog RW. Gene Ther 2010;17(3):295–304.
  2. Bessis N, et al. Gene Ther 2004;11:S10–S17.