Data from Development of an Anti-canine PD-L1 Antibody and Caninized PD-L1 Mouse Model as Translational Research Tools for the Study of Immunotherapy in Humans Article Swipe

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Wonkyung Oh , Alyssa Min Jung Kim , Deepika Dhawan , Perry M. Kirkham , Raluca Ostafe , Jackeline Franco , Uma K. Aryal , Robert H. Carnahan , Valery Patsekin , J. Paul Robinson , Deborah W. Knapp , Seung‐Oe Lim ·

YOU? · · 2023 · Open Access · · DOI: https://doi.org/10.1158/2767-9764.c.6647231

Immune checkpoint blockade therapy, one of the most promising cancer immunotherapies, has shown remarkable clinical impact in multiple cancer types. Despite the recent success of immune checkpoint blockade therapy, however, the response rates in patients with cancer are limited (∼20%–40%). To improve the success of immune checkpoint blockade therapy, relevant preclinical animal models are essential for the development and testing of multiple combination approaches and strategies. Companion dogs naturally develop several types of cancer that in many respects resemble clinical cancer in human patients. Therefore, the canine studies of immuno-oncology drugs can generate knowledge that informs and prioritizes new immuno-oncology therapy in humans. The challenge has been, however, that immunotherapeutic antibodies targeting canine immune checkpoint molecules such as canine PD-L1 (cPD-L1) have not been commercially available. Here, we developed a new cPD-L1 antibody as an immuno-oncology drug and characterized its functional and biological properties in multiple assays. We also evaluated the therapeutic efficacy of cPD-L1 antibodies in our unique caninized PD-L1 mice. Together, these in vitro and in vivo data, which include an initial safety profile in laboratory dogs, support development of this cPD-L1 antibody as an immune checkpoint inhibitor for studies in dogs with naturally occurring cancer for translational research. Our new therapeutic antibody and caninized PD-L1 mouse model will be essential translational research tools in raising the success rate of immunotherapy in both dogs and humans.Significance:Our cPD-L1 antibody and unique caninized mouse model will be critical research tools to improve the efficacy of immune checkpoint blockade therapy in both dogs and humans. Furthermore, these tools will open new perspectives for immunotherapy applications in cancer as well as other autoimmune diseases that could benefit a diverse and broader patient population.

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Immune checkpoint Immunotherapy Medicine Cancer immunotherapy Blockade Antibody Cancer Immune system Immunology Translational research Cancer research Clinical trial PD-L1 Oncology In vivo Internal medicine Biology Receptor Pathology Biotechnology

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Type: preprint
Language: en
Landing Page: https://doi.org/10.1158/2767-9764.c.6647231
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DOI: https://doi.org/10.1158/2767-9764.c.6647231

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Title: Data from Development of an Anti-canine PD-L1 Antibody and Caninized PD-L1 Mouse Model as Translational Research Tools for the Study of Immunotherapy in Humans

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Type: preprint

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Language: en

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Publication year: 2023

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Publication date: 2023-05-15

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Authors: Wonkyung Oh, Alyssa Min Jung Kim, Deepika Dhawan, Perry M. Kirkham, Raluca Ostafe, Jackeline Franco, Uma K. Aryal, Robert H. Carnahan, Valery Patsekin, J. Paul Robinson, Deborah W. Knapp, Seung‐Oe Lim

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Landing page: https://doi.org/10.1158/2767-9764.c.6647231

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Concepts: Immune checkpoint, Immunotherapy, Medicine, Cancer immunotherapy, Blockade, Antibody, Cancer, Immune system, Immunology, Translational research, Cancer research, Clinical trial, PD-L1, Oncology, In vivo, Internal medicine, Biology, Receptor, Pathology, Biotechnology

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abstract_inverted_index.raising	217
abstract_inverted_index.several	70
abstract_inverted_index.studies	87, 191
abstract_inverted_index.success	23, 43, 219
abstract_inverted_index.support	179
abstract_inverted_index.testing	59
abstract_inverted_index.therapy	100, 248
abstract_inverted_index.(cPD-L1)	120
abstract_inverted_index.antibody	132, 184, 204, 229
abstract_inverted_index.blockade	2, 27, 47, 247
abstract_inverted_index.clinical	14, 79
abstract_inverted_index.critical	237
abstract_inverted_index.diseases	271
abstract_inverted_index.efficacy	152, 243
abstract_inverted_index.generate	92
abstract_inverted_index.however,	29, 107
abstract_inverted_index.multiple	17, 61, 145
abstract_inverted_index.patients	34
abstract_inverted_index.relevant	49
abstract_inverted_index.research	214, 238
abstract_inverted_index.resemble	78
abstract_inverted_index.respects	77
abstract_inverted_index.response	31
abstract_inverted_index.therapy,	3, 28, 48
abstract_inverted_index.Companion	66
abstract_inverted_index.Together,	162
abstract_inverted_index.caninized	159, 206, 232
abstract_inverted_index.challenge	104
abstract_inverted_index.developed	128
abstract_inverted_index.essential	54, 212
abstract_inverted_index.evaluated	149
abstract_inverted_index.inhibitor	189
abstract_inverted_index.knowledge	93
abstract_inverted_index.molecules	115
abstract_inverted_index.naturally	68, 195
abstract_inverted_index.occurring	196
abstract_inverted_index.patients.	83
abstract_inverted_index.promising	8
abstract_inverted_index.research.	200
abstract_inverted_index.targeting	111
abstract_inverted_index.Therefore,	84
abstract_inverted_index.antibodies	110, 155
abstract_inverted_index.approaches	63
abstract_inverted_index.autoimmune	270
abstract_inverted_index.available.	125
abstract_inverted_index.biological	142
abstract_inverted_index.checkpoint	1, 26, 46, 114, 188, 246
abstract_inverted_index.functional	140
abstract_inverted_index.laboratory	177
abstract_inverted_index.properties	143
abstract_inverted_index.remarkable	13
abstract_inverted_index.<i>in	164, 167
abstract_inverted_index.combination	62
abstract_inverted_index.development	57, 180
abstract_inverted_index.preclinical	50
abstract_inverted_index.prioritizes	97
abstract_inverted_index.strategies.	65
abstract_inverted_index.therapeutic	151, 203
abstract_inverted_index.Furthermore,	254
abstract_inverted_index.applications	263
abstract_inverted_index.commercially	124
abstract_inverted_index.perspectives	260
abstract_inverted_index.characterized	138
abstract_inverted_index.immunotherapy	222, 262
abstract_inverted_index.translational	199, 213
abstract_inverted_index.vivo</i>	168
abstract_inverted_index.(∼20%–40%).	39
abstract_inverted_index.immuno-oncology	89, 99, 135
abstract_inverted_index.vitro</i>	165
abstract_inverted_index.immunotherapies,	10
abstract_inverted_index.immunotherapeutic	109
abstract_inverted_index.<div><p>Immune	0
abstract_inverted_index.population.</p></div>	280
abstract_inverted_index.humans.</p>Significance:<p>Our	227
cited_by_percentile_year
countries_distinct_count	0
institutions_distinct_count	12
citation_normalized_percentile.value	0.28968947
citation_normalized_percentile.is_in_top_1_percent	False
citation_normalized_percentile.is_in_top_10_percent	False