Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Cancer cell or component thereof
Reexamination Certificate
2000-04-05
2003-08-05
Schwadron, Ronald B. (Department: 1644)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Cancer cell or component thereof
C530S324000, C530S325000, C530S326000, C530S327000, C530S328000, C530S402000, C424S192100, C424S193100, C424S450000, C424S093710, C514S002600, C514S015800, C514S014800, C514S013800, C514S012200
Reexamination Certificate
active
06602510
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to the field of biology. In a particular embodiment, it relates to compositions useful to monitor or elicit an immune response to selected tumor-associated antigens.
Index
I. Background of the Invention
II. Summary of the Invention
III. Brief Description of the Figures
IV. Detailed Description of the Invention
A. Definitions
B. Stimulation of CTL and HTL responses
C. Binding Affinity of Peptide Epitopes for HLA Molecules
D. Peptide Epitope Binding Motifs and Supermotifs
1. HLA-A2 supermotif
2. HLA-A2.1 motif
3. HLA Class II Motifs and PADRE™
E. Enhancing Population Coverage of the Vaccine
F. Immune Response-Stimulating Peptide Epitope Analogs
G. Preparation of Peptide Epitopes
H. Assays to Detect T-Cell Responses
I. Use of Peptide Epitopes for Evaluating Immune Responses
J. Vaccine Compositions
1. Minigene Vaccines
2. Combinations of CTL Peptides with Helper Peptides
3. Combinations of CTL Peptides with T Cell Priming Materials
4. Vaccine Compositions Comprising Dendritic Cells Pulsed with CTL and/or HTL Epitopes
K. Administration of Vaccines for Therapeutic or Prophylactic Purposes
L. Kits
V. Examples
VI. Claims
VII. Abstract
I. BACKGROUND OF THE INVENTION
The field of immunotherapy is yielding new approaches for the treatment of cancer, including the development of improved cancer vaccines (Krul, K. G.,
Decision Resources,
10.1-10.25 (1998)). While vaccines provide a mechanism of directing immune responses towards the tumor cells, there are a number of mechanisms by which tumor cells circumvent immunological processes (Pardoll, D. M.,
Nature Medicine
(Vaccine Supplement), 4:525-531 (1998)). Recent advances indicate that the efficacy of peptide vaccines may be increased when combined with approaches which enhance the stimulation of immune responses, such as the use of Interleukin-2 or autologous dendritic cells (DC) (Abbas et al., eds.,
Cellular and Molecular Immunology,
3
rd
Edition, W. B. Saunders Company, pub. (1997)).
In a Phase I study, Murphy, et al., demonstrated that Human Leukocyte Antigen (HLA)-A2-binding peptides corresponding to sequences present in prostate specific antigen (PSA) stimulated specific cytotoxic T-cell lymphocyte (CTL) responses in patients with prostate cancer (Murphy et al.,
The Prostate
29:371-380 (1996)). Recently, Rosenberg, et al., evaluated the safety and mechanism of action of a synthetic HLA-A2 binding peptide derived from the melanoma associated antigen, gp100, as a cancer vaccine to treat patients with metastatic melanoma (Rosenberg et al.,
Nature Med.,
4:321-327 (1998)). Based on immunological assays, 91% of patients were successfully immunized with the synthetic peptide. In addition, 42% (13/31) of patients who received the peptide vaccine in combination with IL-2 treatment, demonstrated objective cancer responses. Finally, Nestle, et al., reported the vaccination of 16 melanoma patients with peptide- or tumor lysate-pulsed DC (Nestle et al.,
Nature Med
4:328-332 (1998)). Peptide-pulsed DC induced immune responses in (11/12) patients immunized with a vaccine comprised of 1-2 peptides. Objective responses were evident in 5/16 (3 peptide-pulsed, 2 tumor-lysate pulsed) evaluated patients in this study. These Phase I safety studies provided evidence that HLA-A2 binding peptides of known tumor-associated antigens demonstrate the expected mechanism of action. These vaccines were generally safe and well tolerated. Vaccine molecules related to four cancer antigens, CEA, HER2
eu, MAGE2, and, MAGE3 have been disclosed. (Kawashima et al.,
Human Immunology,
59:1-14 (1998)).
Preclinical studies have shown that vaccine-pulsed DC mediate anti-tumor effects through the stimulation of antigen-specific CTL (Mandelboim et al.,
Nature Med.,
1: 1179-1183 (1995); Celluzzi et al.,
J Exp Med
183:283-287 (1996); Zitvogel et al.,
J Exp Med
183:87-97 (1996); Mayordomo et al.,
Nature Med
1:1297-1302 (1995)). CTL directly lyse tumor cells and also secrete an array of cytokines such as interferon gamma (IFN&ggr;), tumor necrosis factor (TNF) and granulocyte-macrophage colony stimulating factor (GM-CSF), that further amplify the immune reactivity against the tumor cells. CTL recognize tumor associated antigens (TAA) in the form of a complex composed of 8-11 amino acid residue peptide epitopes, bound to Major Histocompatibility Complex (MHC) molecules (Schwartz, B. D.,
The human major histocompatibility complex HLA in basic
&
clinical immunology
Stites et al., eds., Lange Medical Publication: Los Altos, pp. 52-64, 4
th
ed.). Peptide epitopes are generated through intracellular processing of
3
proteins. The processed peptides bind to newly synthesized MHC molecules and the epitope-MHC complexes are expressed on the cell surface. These epitope-MHC complexes are recognized by the T cell receptor of the CTL. This recognition event is required for the activation of CTL as well as induction of the effector functions such as lysis of the target tumor cell.
MHC molecules are highly polymorphic proteins that regulate T cell responses (Schwartz, B. D.,
The human major histocompatibility complex HLA in basic
&
clinical immunology
Stites et al., eds., Lange Medical Publication: Los Altos, pp. 52-64, 4
th
ed.). The species-specific MHC homologues that display CTL epitopes in humans are termed HLA. HLA class I molecules can be divided into several families or “supertypes” based upon their ability to bind similar repertoires of peptides. Vaccines which bind to HLA supertypes such as A2, A3, and B7, will afford broad, non-ethnically biased population coverage. As seen in Table 11, population coverage is 84-90% for various ethnicities, with an average coverage of the sample ethnicities at 87%.
Various approaches have, or are, being employed as cancer vaccines. Table 1 overviews the major cancer vaccine approaches and the various advantages and disadvantages of each.
Currently there are a number of unmet needs in the area of cancer treatment. This is evidenced by the side effects associated with existing therapies employed for cancer treatment and the fact that less than 50% of patients are cured by current therapies. Therefore, an opportunity exists for a product with the ability to either increase response rates, duration of response, overall survival, disease free survival or quality of life.
II. SUMMARY OF THE INVENTION
Disclosed herein is a composition comprising all eight isolated epitopes: YLSGANLNV (SEQ ID NO:1), IMIGVLVGV (SEQ ID NO:2), KLBPVQLWV (SEQ ID NO:3), SMPPPGTRV (SEQ ID NO:4), KVAELVHFL (SEQ ID NO:5), YLQLVFGIEV (SEQ ID NO:6), RLLQETELV (SEQ IS NO:7), and VVLGVVFGI (SEQ ID NO:8). The composition can further comprise an antigen presenting cell, whereby at least one epitope is bound to an HLA molecule on the antigen presenting cell, such that a T lymphocyte receptor can bind to a complex of the HLA molecule and the epitope. The antigen presenting cell can be a dendritic cell. The composition can comprise each epitope connected to another epitope by peptide bonds. An amino acid linker can be a component of the composition, wherein at least two of the epitopes are connected to each other by peptide bonds. The composition can comprise a CTL or HTL epitope; the HTL epitope can be a pan-DR binding molecule. The composition can comprise a liposome, wherein the epitopes are on or within the liposome. A lipid can be attached to one of the epitopes.
In another embodiment, a composition can comprise at least one peptide, the peptide comprising an isolated, prepared epitope consisting of a sequence selected from the group consisting of: VLYGPDAPTV (SEQ ID NO:9), YLSGANLNV (SEQ ID NO:1), ATVGIMIGV (SEQ ID NO:10), LLPENNVLSPV (SEQ ID NO:11), KLCPVQLWV (SEQ ID NO:12), KLBPVQLWV (SEQ ID NO:3), SLPPPGTRV (SEQ ID NO:13), SMPPPGTRV (SEQ ID NO:4), KLFGSLAFV (SEQ ID NO:14), KVFGSLAFV (SEQ ID NO:15), VMAGVGSPYV (SEQ ID NO:16), ALCRWGLLL (SEQ ID NO:17), FLWGPPALV (SEQ ID NO:18), HLYQGCQVV (SEQ ID NO:19), ILHNGAYSL (SEQ ID NO:20), IMIGVLVGV (SEQ ID NO:2), KIFGSLAFL (SEQ ID NO:21), KVAELVHFL (SEQ ID NO:5), LLTFWN
Celis Esteban
Chesnut Robert
Fikes John D.
Keogh Elissa A.
Sette Alessandro
Epimmune Inc.
Schwadron Ronald B.
Sterne Kessler Goldstein & Fox P.L.L.C.
LandOfFree
HLA class I A2 tumor associated antigen peptides and vaccine... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with HLA class I A2 tumor associated antigen peptides and vaccine..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and HLA class I A2 tumor associated antigen peptides and vaccine... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3116696