Publications

ISA Pharmceuticals regularly publishes its findings and data in peer-reviewed journals.

Please find below a list of key publications grouped by topic:

SLP® Technology

Key publications:

van der Sluis T, et al., Melief CJ, Arens R, van der Burg SH, van Hall T “Therapeutic peptide vaccine-induced CD8 T cells strongly modulate intratumoral macrophages required for tumor regression.” Can Immunol Res.; Sep;3(9):1042-51. Describes that administration of SLP immunotherapeutics can induce cytokine-producing T cells with the strong macrophage-skewing capacity necessary for tumor shrinkage.

Gubin MM, et al.,  Melief CJ, Mardis ER, Gillanders WE, Artyomov MN, Schreiber RD. “Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens.” Nature. 2014 Nov 27;515(7528):577-81. One of the first key papers setting the scene for developing individualized cancer vaccines, an emerging area where ISA is currently one of the leaders. It is co-authored by our CSO prof Melief and applies our proprietary SLP technology.

Rosalia et al.; Melief CJ. “Dendritic cells process synthetic long peptides better than whole protein, improving antigen presentation and T-cell activation.” Eur J Immunol.; 2013 Oct;43(10):2554-65. doi: 10.1002/eji.201343324. Epub 2013 Aug 5. Provides the background for choosing the SLP technology as our backbone as it is clearly superior to other modalities.

 

AMPLIVANT® Technology

Key publication:

Zom GG, et al.  Melief CJ, van der Burg SH, Ossendorp F. “TLR2 ligand-synthetic long peptide conjugates effectively stimulate tumor-draining lymph node T cells of cervical cancer patients.Oncotarget. 2016 Aug;10.18632/oncotarget.11512. Describes the improved immunogenicity of conjugation of AMPLIVANT to two HPV16-E6 SLPs, for which safety and immunogenicity is currently studied in a Phase I trial HESPECTA trial.

 

ISA101

Key publications:

Welters MJ, van der Sluis TC, van Meir H, et. al., Melief CJ, van der Burg SH. “Vaccination during myeloid cell depletion by cancer chemotherapy fosters robust T cell responses.” Sci Transl Med. 2016 Apr 13;8(334):334ra52. Describes the outcome of the clinical pilot study in cervical cancer, combining ISA101 with chemotherapy.

van Poelgeest MI, et al., Melief CJ, van der Burg SH. “Vaccination against oncoproteins of HPV16 for non-invasive vulvar/vaginal lesions: lesion clearance is related to the strength of the T-cell response.” Clin Cancer Res 2016 May 15;22(10):2342-50. Demonstrates that vaccination with ISA101 induces objective partial or complete histological regression of the lesion in more than 50% of the patients and as such is an effective means to treat VIN that may prevent surgical mutilation.

Van der Sluis TC, et al., Melief CJ. “Vaccine-induced Tumor Necrosis Factor producing T-cells synergize with cisplatin to promote tumor cell death.Clin Cancer Res. 2015 21(4): 781-794. Describes the mechanism of the synergy of peptide vaccination with cisplatin, which render tumor cells more susceptible to cisplatin-mediated apoptosis.

Kenter GG, et al., Melief CJ. “Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia.N Engl J Med. 2009 Nov 5;361(19):1838-47. Describes the proof-of-concept established in our first trial in HPV-16 induced pre-cancerous neoplasia. ISA was the first to demonstrate a correlation between immune responses and clinical responses.

 

Immunotherapy & Immunology Expertise

Key publications:

van der Burg et al. SH, Melief CJ “Vaccines for established cancer: overcoming the challenges posed by immune evasion.” Nat Rev Cancer 2016,  219–233  (2016). Provides a comprehensive overview of the known immune suppressive mechanisms and how to neutralize them.

Melief CJ, et al., “Therapeutic Cancer Vaccines.” J Clin Invest 2015 125 (9):3401-12. Provides an overview and key insights of the state-of-the-art in therapeutic cancer vaccines.