Monoclonal canine CD20 antibodies and methods of use
View Patent ↗This disclosure relates to immunogens and monoclonal antibodies useful in the identification and/or treatment of cancer cells, including those of the dog. In one example, chimeric anti-canine CD20 antibodies are provided. The antibodies can be used therapeutically to treat lymphoma in dogs.
1. An isolated monoclonal antibody that binds canine CD20, the antibody comprising at least one set of variable region amino acid sequences selected from the group consisting of:
a light chain variable region (LC-V) comprising the sequence of
(SEQ ID NO.: 3)
DVVMTQNPLSLPVSLGDQASISCRSSQSLIYNNGNTYLHWYRQKPGQSPK
LLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQSTHVP
FTFGSGTKLEIK
and a heavy chain variable region (HC-V) comprising the sequence of
(SEQ ID NO.: 6)
EVQLVESGGGLVKPGGSLKLSCAASGFTFSDYGMLWVRQAPEKGLEWIAY
ISSGSSTIYYADRVKGRFTISRDNAKNTLFLQMTSLRSEDTAMYYCSTGT
FAYWGQGTPVTVSS;
an LC-V comprising the sequence of
(SEQ ID NO.: 9)
DIVMTQAAPSVPVTPGESVSISCRSNKSLLHRNGNTYLYWFLQRPGQSPQ
LLIYRMSNLASGVPDRFSGSGSGTAFTLRISRVEAEDVGVYYCMQHLEFP
FTFGGGTKLEIK
and a HC-V comprising the sequence of
(SEQ ID NO.: 11)
EVQLQQSGPELVKPGASVKISCKASGYTFTDYYMNWVKQSHGKSLEWIGD
INPNNGDTSYNQKFKGKAPLTVDKSSSTAYMEVRSLTSEDSAVYFCARGG
VLRYPYYYVMDYWGQGTSVTVSS;
and an LC-V comprising the sequence of
(SEQ ID NO.: 13)
DIVMTQSQKFMSRSVGDRVSVTCKASQNVGPNVAWYQQRPGQSPKPLIY
SASYRYSGVPDRFTGSGSGTDFTLTISNVQSEDLAEYFCQQYNNYPYTF
GGGTKLEIK
and a HC-V comprising the sequence of
(SEQ ID NO.: 15)
EVQLQQSGAELVRPGASVKLSCTASGFNIKDDYMHWVKQRPEQGLEWIG
WIDPENGHTKYASKFQGKATITADTSSNTAYLQLSSLTSEDTAVYYCTS
LRHYYGSSYVSPHYYWGQGTTLTVSS;
wherein the antibody binds canine CD20.
2. The monoclonal antibody of claim 1 , wherein the antibody comprises at least one light chain immunoglobulin constant region amino acid sequence from canine, and at least one heavy chain immunoglobulin constant region amino acid sequence from canine.
3. The monoclonal antibody of claim 2 , wherein the at least one light chain immunoglobulin constant region amino acid sequence from canine comprises at least one of the amino acid sequences selected from the group consisting of:
(SEQ ID NO.: 55)
RNDAQPAVYLFQPSPDQLHTGSASVVCLLNSFYPKDINVKWKVDGVIQD
TGIQESVTEQDKDSTYSLSSTLTMSSTEYLSHELYSCEITHKSLPSTLI
KSFQRSECQRVD,
(SEQ ID NO.: 78)
RTDAQPAVYLFQPSPDQLHTGSASVVCLLNSFYPKDINVKWKVDGVIQD
TGIQESVTEQDKDSTYSLSSTLTMSSTEYLSHELYSCEITHKSLPSTLI
KSFQRSECQRVD,
(SEQ ID NO.: 79)
RNDAQPAVYLFQPSPDQLHTGSASVVCLLSSFYPKDINVKWKVDGVIQD
TGIQESVTEQDKDSTYSLSSTLTMSSTEYLSHELYSCEITHKSLPSTLI
KSFQRSECQRVD,
and
(SEQ ID NO.: 80)
RTDAQPAVYLFQPSPDQLHTGSASVVCLLSSFYPKDINVKWKVDGVIQD
TGIQESVTEQDKDSTYSLSSTLTMSSTEYLSHELYSCEITHKSLPSTLI
KSFQRSECQRVD;
and wherein the at least one heavy chain immunoglobulin constant region amino acid sequence from canine comprises at least one of the amino acid sequences selected from the group consisting of:
(SEQ ID NO.: 57)
ASTTAPSVFPLAPSCGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG
VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASKTKVDKPV
PKRENGRVPRPPDCPKCPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTC
VVVDLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYRVVSVLPIGH
QDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELS
KNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFL
YSKLSVDKSRWQRGDTFICAVMHEALHNHYTQKSLSHSPGK,
(SEQ ID NO.: 81)
ASTTAPSVFPLAPSCGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG
VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASKTKVDKPV
PKRENGRVPRPPDCPKCPAPEPAGGPSVFIFPPKPKDTLLIARTPEVTC
VVVDLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYRVVSVLPIGH
QDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELS
KNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFL
YSKLSVDKSRWQRGDTFICAVMHEALHNHYTQKSLSHSPGK,
(SEQ ID NO.: 82)
ASTTAPSVFPLAPSCGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG
VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASKTKVDKPV
PKRENGRVPRPPDCPKCPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTC
VVVDLDPEDPEVQISWFVDGKQMQTAKTQPREEQFAGTYRVVSVLPIGH
QDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELS
KNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFL
YSKLSVDKSRWQRGDTFICAVMHEALHNHYTQKSLSHSPGK,
and
(SEQ ID NO.: 83)
ASTTAPSVFPLAPSCGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG
VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASKTKVDKPV
PKRENGRVPRPPDCPKCPAPEAAGGPSVFIFPPKPKDTLLIARTPEVTC
VVVDLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYRVVSVLPIGH
QDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELS
KNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFL
YSKLSVDKSRWQRGDTFICAVMHEALHNHYTQKSLSHSPGK.
4. A method for treating a canine CD20-expressing lymphoma in a canine animal comprising administering to the animal at least one effective dose of the monoclonal antibody of claim 1 .
5. The method of claim 4 wherein the monoclonal antibody is administered in a dosage amount of about 1 to 50 mg/kg of body weight of the animal.
6. The method of claim 4 wherein multiple doses are administered to the animal.
7. The method of claim 4 wherein the monoclonal antibody is administered in conjunction with one or more chemotherapeutic agents.