PXD020304

PXD020304 is an original dataset announced via ProteomeXchange.

Title	Regression of breast cancer metastases following treatment with irradiated SV-BR-1-GM, a GM-CSF overexpressing breast cancer cell line: clinical, molecular, and immune markers of response
Description	BACKGROUND: While many authorities theorize that cancer vaccines are too weak to be widely effective, there are quite a few reports with clearly demonstrated, significant clinical benefit in some patients. The literature of cellular cancer immunotherapies shows that 53% (78/147) of phase II studies showed evidence of clinical activity. While not all reached their primary endpoints, 75% (12/16) of phase III studies had positive data. SV-BR-1-GM, derived from a patient with grade 2 (moderately differentiated) breast cancer, is a GM-CSF-secreting breast cancer cell line with properties of antigen-presenting cells we established. METHODS: We report detailed molecular and clinical findings from an open-label phase I, single-arm pilot study in breast (3 subjects) and ovarian (1 subject) cancer with irradiated SV-BR-1-GM cells (ClinicalTrials.gov Identifier NCT00095862). Inoculations of SV-BR-1-GM were preceded by low-dose cyclophosphamide and followed by injections of interferon-alpha2b into the SV-BR-1-GM inoculation sites. We assessed both cellular (delayed-type hypersensitivity (DTH) reactions) and humoral (anti-SV-BR-1 antibody) immune responses and conducted molecular analyses on patient blood cells and SV-BR-1-GM cells. RESULTS: Treatment was generally safe and well tolerated. Immune responses were elicited universally. Overall survival was more than 33 months for three of the four patients. As previously reported, one patient (Subject A002, with grade 2 breast cancer) had regression of metastases in lung, breast and soft tissue within 2 months of treatment initiation. At later relapse, with multiple metastases including several in the brain, rapid tumor response was again seen, including complete regression of CNS metastases. Consistent with a role of Class II HLA in contributing to SV-BR-1-GM’s mechanism of action, Subject A002 allele-matched SV-BR-1-GM at the HLA-DRB1 and HLA-DRB3 loci. Only the HLA-DRB1 alleles were clearly expressed in SV-BR-1-GM cells. However, interferon-gamma (possibly also present in situ) upregulated both HLA-DRB1 and HLA-DRB3 to substantial levels. Gene expression data supports the hypothesis that SV-BR-1-GM cells have retained some of the original breast cancer’s grade 2 character. CONCLUSIONS: We describe a whole-cell immunotherapy regimen with remarkable rapidity of response and a speedy rescue response, including complete resolution of CNS metastases after relapse. Class II HLA matches might be critical for SV-BR-1-GM’s therapeutic potential.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:37:51.160.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vito Dozio
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-10 03:46:33	ID requested
1	2022-06-22 18:10:43	announced
⏵ 2	2024-10-22 05:37:51	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: GVAX, Whole-cell vaccine, Therapeutic cancer vaccine, Targeted immunotherapy, Antigen-presenting cells,SV-BR-1-GM

Markus D. Lacher
contact affiliation	BriaCell Therapeutics Corporation, Berkeley, CA, USA
contact email	mlacher@briacell.com
lab head
Vito Dozio
contact affiliation	Biognosys SA
contact email	vito.dozio@biognosys.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020304
     1. Label: PRIDE project
     2. Name: Regression of breast cancer metastases following treatment with irradiated SV-BR-1-GM, a GM-CSF overexpressing breast cancer cell line: clinical, molecular, and immune markers of response