publications

Massarelli E et al., Melief CJ, Glisson B. “Combining Immune Checkpoint Blockade and Tumor-Specific Vaccine for Patients With Incurable Human Papillomavirus 16-Related Cancer: A Phase 2 Clinical Trial” JAMA Oncol. 2018 Sep 27. [Epub ahead of print]

Describes the outcome of an investigator sponsored trial conducted at MD Anderson Cancer Center in patients suffering from advanced HPV16 positive Head and Neck cancer, combining ISA101 with nivolumab. Data demonstrate that the ORR of 36% in patients with oropharyngeal cancer compares favourably to the ORR of 16% demonstrated for nivolumab monotherapy in patients with p16-positive platin-refractory oropharyngeal cancer participating in the in Checkmate 141 study.

Melief CJ et al. “Strong vaccine responses during chemotherapy are
associated with prolonged cancer survival” Science Translational Medicine 12, March 2020.

Describes the results of the CervISA study. This was an open label, phase 2 study in patients with late stage HPV16 positive cervical cancer. Seventy-seven patients were treated with ISA Pharma’s lead product, ISA101b, an HPV16-specific immunotherapeutic agent, in combination with standard-of-care (SoC) chemotherapy (carboplatin/paclitaxel). The addition of ISA101b to SoC chemotherapy led to a strong and highly specific anti-tumor immune response and significant improvement of patient survival in responding patients .

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 Jan 26;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.

Borst et al., Melief CJM, Kastenmüller W “CD4+ T cell help in cancer immunology and immunotherapy.” Nat Rev Immunol 2018 Oct;18(10):635-647

Review outlining how deficient CD4+ T cell help reduces the response of CTLs and how maximizing CD4+ T cell help can improve outcomes in cancer immunotherapy strategies.

Beyranvand et al., Melief CJ, van der Burg SH, Ahrens R “Tumor Eradication by Cisplatin Is Sustained by CD80/86-Mediated Costimulation of CD8+ T Cells” Cancer Res 2016 Oct 15;76(20):6017-6029

Review on immunogenic properties of cisplatin and its synergy with vaccination and immunomodulation.

van der Burg et al. SH, Melief CJ “Vaccines for established cancer: overcoming the challenges posed by immune evasion” Nat Rev Cancer 2016 Apr; 16(4):219-33

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.

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 2015 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 RA, 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

Provides the background for choosing the SLP technology as our backbone as it is clearly superior to other modalities.

Zom GG, et al.  Melief CJ, Ossendorp F. “Novel TLR2-binding adjuvant induces enhanced T cell responses and tumor eradication” J Immunother Can. 2018 Dec 12;6(1):146.

Describes the mechanism of improved immunogenicity of conjugation of AMPLIVANT. SLPs conjugated to AMPLIVANT induce stronger DC maturation, in vivo T cell priming and antitumor immunity compared to conjugates with Pam3CSK4

Zom GG, et al.  Melief CJ, de Gruijl T, Van der Marel GA, Filippov DV, Ossendorp F, Van der Burg SH. “TLR2 ligand-synthetic long peptide conjugates effectively stimulate tumor-draining lymph node T cells of cervical cancer patients.” Oncotarget. 2016 Oct 11;7(41):67087-67100.

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