Recent advances in the development of breast cancer vaccines

Figures & data

Table 1 Main breast cancer TAAs

Target	Description
Carcinoembryonic antigen	Glycoprotein involved in cell adhesion, normally expressed during fetal development
Human epithelial growth factor receptor 2	Growth factor receptor belonging to human epithelial growth factor receptor family Overexpressed in 20%–30% of breast cancer cells, correlates with adverse prognosis
MUC-1	Membrane glycoprotein involved in immunologic and cell signaling functions Overexpressed in 70% of breast cancers
hTERT	Component of the telomerase complex, a ribonucleoprotein that maintain chromosome integrity during cell proliferation and division
p53	Tumor suppressor protein, involved in cell cycle regulation and DNA damage repair Mutated in 20% of breast cancers
Mammaglobin-A	Glycoprotein overexpressed in 80% of metastatic breast cancers
Cancer testis antigens (NY-eso-1, MAGE, BAGE, and GAGE)	Proteins expressed in normal germ cells of the testis and embryonic ovaries and in certain types of cancer

Abbreviations: TAAs, tumor-associated antigens; hTERT, telomerase reverse transcriptase; MUC-1, mucin-1.

Table 2 Current vaccine platforms

Vaccine platform	Strengths	Possible limitations
Peptide-based vaccines	Easily produced and delivered Low toxicities Easy to monitor immunologic response	Able to elicit mainly one compartment of immunological response (cytotoxic or humoral) Require boosts inoculation to maintain immunological memory HLA-restricted Require suitable adjuvant Response restricted to one or few epitopes
DC-based vaccines	Not HLA restricted Capable to elicit immunological memory, humoral and cytotoxic response	Technically challenging Requires expansion, maturation, and activation of DCs
DNA-based vaccines	Can be produced on larger scales Can elicit both humoral and cytotoxic compartments	Risk of toxicities Low efficiency of naked DNA or plasmids Difficulties in finding suitable vectors
Whole cell-based vaccines	Can elicit a response against broad spectrum of antigens Not HLA-restricted	Difficult to monitor response Risk of toxicities and autoimmunity Requires cell manipulation to be immunogenic

Abbreviations: HLA, human leukocyte antigen; DC, dendritic cell.

Table 3 Clinical trials with anti-HER2 vaccinations

Platform	Vaccine	Setting and number of patients	Adverse events	Results
Protein-based vaccine	HER2 ICD + GM-CSF	Adjuvant, 29 pts	No G2, G3, or G4 toxicities reported	Specific T-cell and antibody were elicited in 89% and 82% of pts, respectively^Citation70
Protein-based vaccine	dHER2 (truncated recombinant HER2 ECD and ICD) + immunoadjuvant	Adjuvant, 45 pts	One G3 fatigue and one G3 neutropenia	HER2 ECD and ICD antibodies developed after four immunizations Two pts showed evidence of tumor regression^Citation72
DNA-based vaccine	Poxviral vector encoding a modified form of the HER2 protein	Metastatic, 30 pts	No G3 or G4 toxicities reported	HER2-specific antibodies and T-cell response were detected in 66% pts (15 out of 28) evaluable patients had SD after 6 months FU^Citation71
Whole cell-based vaccine	SKBR3 (HER2 overexpressing cell line) genetically modified to secrete GM-CSF administered with TReg depleting doses of CY and DOX	Metastatic, 28 pts	No G3 or G4 toxicities reported	Induction of efficient immune response, including specific antibody production, enhanced by CY and DOX^Citation73

Abbreviations: GM-CSF, granulocyte-macrophage colony-stimulating factor; ECD, extracellular domain; HER2, human epithelial growth factor receptor 2; ICD, intracellular domain; pts, patients; G, grade; BC, breast cancer; MBC, metastatic breast cancer; FU, follow-up; SD, stable disease; TReg, regulatory T lymphocytes; CY, cyclophosphamide; DOX, doxorubicin; SKBR3, human HER2 overexpressing breast cancer cell line.

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