US 12,403,186 B2
Allogeneic tumor cell vaccine
Frank Borriello, Winchester, MA (US)
Assigned to Alloplex Biotherapeutics, Inc., Woburn, MA (US)
Filed by ALLOPLEX BIOTHERAPEUTICS, INC., Woburn, MA (US)
Filed on Apr. 16, 2021, as Appl. No. 17/233,124.
Application 17/233,124 is a division of application No. 15/821,105, filed on Nov. 22, 2017, granted, now 11,058,752.
Claims priority of provisional application 62/425,424, filed on Nov. 22, 2016.
Prior Publication US 2021/0236610 A1, Aug. 5, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 39/00 (2006.01); A61P 35/00 (2006.01); C07K 14/525 (2006.01); C07K 14/535 (2006.01); C07K 16/44 (2006.01); C12N 5/09 (2010.01)
CPC A61K 39/0011 (2013.01) [A61K 39/001129 (2018.08); A61K 39/001138 (2018.08); A61K 39/001139 (2018.08); A61P 35/00 (2018.01); C07K 14/525 (2013.01); C07K 14/535 (2013.01); C07K 16/44 (2013.01); C12N 5/0693 (2013.01); A61K 2039/5152 (2013.01); A61K 2039/5156 (2013.01); C07K 2317/524 (2013.01); C07K 2317/53 (2013.01); C07K 2317/56 (2013.01); C07K 2317/622 (2013.01); C07K 2317/72 (2013.01); C12N 2501/25 (2013.01); C12N 2501/52 (2013.01)] 5 Claims
 
1. An allogeneic tumor cell vaccine used to elicit and stimulate an immune response against a melanoma or prostate cancer comprising:
(1) a clonally-derived variant of a melanoma tumor cell line or a prostate tumor cell line comprising:
(a) two or more stably expressed recombinant membrane-bound immunomodulator molecules selected from the group consisting of an IgG1 peptide, a CD40L peptide, a TNF-alpha peptide, and an Flt-3L peptide; and
(b) a stably expressed recombinant soluble GM-CSF peptide; and
(2) a pharmaceutically acceptable carrier;
wherein the clonally-derived variant of the melanoma tumor cell line or the prostate tumor cell line is proliferation-incompetent;
wherein the clonally-derived variant of the melanoma tumor cell line or the prostate tumor cell line is effective to elicit stimulation of the immune response to a subject's melanoma or prostate cancer, respectively, comprising activation of one or more of T cells, B cells, and dendritic cells as measured by one or more parameters selected from cellular proliferation, cellular subset differentiation, cytokine release profile, and tumor cell lysis that improves overall survival of the subject when compared to a control comprising a non-transfected melanoma tumor cell line or a prostate tumor cell line;
wherein the clonally-derived variant of the melanoma tumor cell line or the prostate tumor cell line expresses the soluble GM-CSF peptide comprising an amino acid sequence as set forth in SEQ ID NO: 13 and two or more of:
(a) the membrane-bound IgG1 immunomodulator peptide comprising an amino acid sequence as set forth in SEQ ID NO: 45;
(b) the membrane-bound CD40L immunomodulator peptide comprising an amino acid sequence as set forth in SEQ ID NO: 7;
(c) the membrane-bound form of TNF-alpha immunomodulator peptide comprising an amino acid sequence as set forth in SEQ ID NO: 11; and
(d) the membrane-bound form of Flt-3L immunomodulator peptide comprising an amino acid sequence as set forth in SEQ ID NO: 14;
wherein the melanoma tumor cell line is SK-MEL2, NIS-G, TRI-G, WIL-G, MRI-H-121B, MRI-H-187, MRI-H-221, or MRI-H-255; and
wherein the prostate tumor cell line is CWR-22, DU145, PC-3/M, PC-3, VCaP, MDA PCa 2b, or LNCaP clone FGC.