ʻAʻohe-Small Cell Lung Cancer: New Preclinical Data

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Hōʻike nā hualoaʻa e hiki ke hana pū me ka mesothelin-targeted TriKE me ka maʻamau o ka mālama o kēia manawa a hāʻawi i ka pōmaikaʻi ʻoiai i loko o ke kaiapuni hypoxic o kahi ʻōpū paʻa.

ʻO GT Biopharma, Inc., kahi hui immuno-oncology i ke kahua lapaʻau i kālele ʻia i ka hoʻomohala ʻana i nā lāʻau lapaʻau hou e pili ana i ka hui o ka hui tri-specific natural killer (NK) cell engager, TriKE® protein biologic platform platform, i hōʻike i ka ʻikepili preclinical e hōʻike ana i kāna puke TriKE hoʻokele NK. cell immunotherapy e kūʻē i ka maʻi maʻi ʻaʻai ʻāʻī liʻiliʻi liʻiliʻi (NSCLC) i ka hypoxic solid tumor microenvironment ma ESMO's Targeted Anticancer Therapies Congress (TAT).

Ua ʻōlelo ʻo Gregory Berk, MD, ka Pelekikena o ka R&D a me ka Luna Lapaʻau Nui o ka Hui, "Ke hōʻike nei kēia hōʻike pre-clinical, ʻoiai ka ʻokoʻa o ka neʻe ʻana o nā cell immune o Stage IVB NSCLC maʻi, hiki i kahi mesothelin-targeted TriKE ke hana pū me ka maʻamau o ka mālama ʻana. Hāʻawi i ka pōmaikaʻi ʻoiai i loko o ke kaiapuni hypoxic o kahi maʻi maʻi paʻa, e pono ai ka hoʻokolokolo hou ʻana o kēia puke, i kuhikuhi ʻia ʻo TriKE.

Ke hoʻokele nei i ka immunotherapy cell NK e kūʻē i ka NSCLC, ma ke ʻano o ka hypoxia, me ka hoʻohana ʻana i ka Tri-specific Killer Engager (TriKE®)

Ka hope - I kēia manawa, ke hoʻāʻo ʻia nei ka Tri-specific killer engagers (TriKE®) ma ke keʻena lapaʻau e mālama i ka maʻi leukemia a me ka lymphoma. ʻO kēia TriKE's cross-link CD16/FcγRIII a me ka antigen tumo ma nā pūnaewele NK e hoʻokau i ka cytotoxicity ʻoiai ʻo IL15 e hāʻawi i nā hōʻailona ola a me ka hoʻonui ʻana i nā cell NK. ʻO Mesothelin (MSLN), i kēia manawa he antigen tumo i kuhikuhi ʻia i nā maʻi maʻi like ʻole me ka NSCLC. ʻO ka haʻawina o kēia manawa i mālama ʻia e ka hale hana ʻo Dr. Jeff Miller, University of Minnesota, i loiloi inā hiki i kahi TriKE i hoʻopaʻa ʻia e MSLN ke hoʻokele i ka cytotoxicity i nā cell NSCLC ma nā pae āpau o ka maʻi i ke alo o ka hypoxia, kahi paʻakikī i ka microenvironment tumor NSCLC.

E aʻo i ka hoʻolālā a me ka nānā ʻana - Ke hoʻohana nei i nā cell mononuclear blood peripheral (PBMC) i hōʻiliʻili ʻia mai nā maʻi NSCLC, (1) ma mua o ka hoʻomaka ʻana o ka mālama maʻamau, (2) ma hope o ka mālama mua ʻana a me (3) i ka piʻi ʻana o ka maʻi inā pili. Ua ho'āʻo ka haʻawina i ka mea maʻi PBMC me kahi laina kelepona NSCLC (NCI-H460) no 5 mau hola i mua o ka monensin a me brefeldin A, ke ana ʻana i ka degranulation (CD107a) a me ka hana cytokine (IFNγ) ma ke kahe cytometry (ola, hoʻokahi CD56 +/CD3- nā pūnaewele. ). Hoʻohālikelike ʻia me nā pūnaewele NK wale nō (NT); ʻO nā pūnaewele NK wale nō me ka lāʻau ('TriKE'); a i ʻole nā ​​pūnaewele NK me ke koko wale nō.

Results

Ua hoʻololi ʻo NSLC i nā pūnaewele NK - Ua hoʻohana ʻia ka hoʻohana ʻana i nā pūʻulu maʻi maʻi ʻokoʻa ʻokoʻa o nā subset immune i ka wā mua a i ʻole ka hopena hope me ka hoʻohana ʻana i ka polokalamu Astrolabe Diagnostics. Ua hiki i ka TriKE ke hoʻoulu i ka hana koʻikoʻi (p<0.0001) e kū'ē i nā pūnaewele H460 no nā hui ʻelua. Ua hōʻike ʻia ka hōʻike ʻana i ka nui o nā pūnaewele CD56+/CD16+ NK a me ka liʻiliʻi o nā pūnaewele CD33+/CD14-myeloid i nā maʻi maʻi mua i hoʻohālikelike ʻia me nā maʻi ma mua o ka hoʻomaka ʻana o ka mālama ʻana. ʻO ka nele o CD16, ka mea e hoʻoneʻe ai i ka cytotoxicity, a me ka nui o nā pūnaewele myeloid, hiki ke hoʻopau i ka hana cell NK, manaʻo ʻia e pane ʻokoʻa nā mea maʻi NSCLC i nā mea olaola e kuhikuhi ana i ka cytotoxicity cell NK.

ʻO TriKE i hoʻopaʻa ʻia e Mesothelin e alakaʻi i ka hana cell NK me ka nānā ʻole i ke kūlana maʻi a ma nā pae āpau o ka mālama ʻana: ʻOiai ʻo ka hypoxia e hōʻino ana i ka cytotoxicity cell NK, ua hoʻonui ʻia ka TriKE i hoʻopaʻa ʻia e MSLN i ka cytotoxicity NK cell o nā maʻi maʻi maʻi maʻi (H460) ma hope o ka ʻike ʻana i ka hypoxia no nā lā 7. , i ka wā e ʻike ai i ka hypoxia a i ka hoʻāʻo ponoʻī. Ua hōʻike ʻia ka ʻikepili ua hoʻokomo ʻo TriKE i ka degranulation a me ka hana cytokine i loko o nā pūnaewele NK maʻi i ka wā i mua o nā cell tumor (H460) ma nā pae āpau o ka mālama ʻana (ma mua o ka mālama ʻana, ma hope o ka mālama mua ʻana a me ka holomua).

Ka hopena - Ke hōʻike nei kēia hōʻike pre-clinical, ʻoiai ka ʻokoʻa o ka neʻe ʻana i nā cell immune o nā maʻi maʻi o Stage IVB NSCLC, hiki i ka mesothelin-targeted TriKE ke hana pū me ke ʻano o ka mālama ʻana i kēia manawa a hāʻawi i ka pōmaikaʻi ʻoiai i loko o ke kaiapuni hypoxic o kahi ʻōpū paʻa.

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Linda Hohnholz

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