Interested Article - LAG3

LAG3 ( ????. Lymphocyte-activation gene 3; CD223 ) — ?????????? ????? ?????????????? ???????????????? , ??????? ???? ???????? LAG3 . ????? LAG3 ??? ?????? ? 1990 ???? . ??????? ??????????????? ?????????????? ????????? ?? ??????? T-?????????? . LAG3 — ???????? ????????? ???-??????, ??????? ???????? ??????? ?????? ???????, ??????????????? ????????????????? ?????????? ? ???????? ????????????? ???????? ?????? ???? ? ???????????? ???????????. ? ???? ????????? ??????????? ????? ??? ?? ???? ???????? ?????????????? ?????????? .

???

??? LAG3 ???????? 8 ??????? . ???????????? ??????????????????, ??????????? ??????? ? ???????? ? ??????????? ??????????? ????????? ?? ??? ???????? ? ????? CD4 . ? ???????? ??? LAG3 ?????????? ?????? CD4 ?? 12-? ????????? (12p13) ? ?? 20 % ????????? ? ?????????

?????

????? LAG3 ??????????? ????????? ?????????????? ???????????????? (Ig). ??????? ?? 503 ??????????? , ???????? 4 ???????????? ???????????????-???????? ??????, ???????????? ? D1 ?? D4. ??? ???????? ????? ? 1990 ???? ? ???? ???? ?????????? ??. 70 % ????????? ? ?????? LAG3 ???? . ????? ???????? ????? ?? 78 % ??????????? ????? ?????? .

???????? ??????????

LAG3 ?????????????? ?? ?????????????? T-??????? , ???????????? ???????? , B-?????????? ? ??????????????? ?????????? ??????? .

???????

???????? ???????? ??? ????????? LAG3 ???????? ????? ???????? ????????? ?????????????????? ?????? II ???-II , ? ???????? ???????? ???????? ????? ??????? ???????????, ??? CD4 . ????? ???????????? ?????????? ????????? ????????????, ????????? ? ????????? T-?????? ?????????? ? CTLA-4 ? PD-1 . ?????? ???? ? ???????????? ?????????? ???????????? ?-?????? .

?????? ??????????? ?? ??????? MHC-II ???????? ????????? ???????? ?????????? ????? .

LAG3 ????????? ? ??????????? CD8 ⁺ -T-?????? ? ???????????? ??????? ? ????????? ?????? ? PD-1, ??????? ?????????? ?????? CD8 ?? ????? ??????????? ???????? ???????? .

LAG3 ????? ?????? ???? ? ?????????? ? ????????? ?????????? ?????? .

? ???????

? ??????????? ???????????? ???????????? ??? ???????, ????????? ? ?????????? LAG3 :

????????? ????? ????? (IMP321) ???????????? ??? ????????, ???????????? ?????????? ?????? .

???????? ? LAG3 ??????????? ??? ?????? ???????????? («????????») ??????????????? ????????? ?????? . ? ????? ????????? ????????? ?????????? (relatlimab), ?????????????? ???????? ? LAG3 , ?????????? ??????????? ????????? . ??? ??????????? ??????? ????????? ? ?????? ????????????? ?????????? . LAG-3 ????? ???? ????? ??????????? ???-???????, ??? CTLA-4 ??? PD-1 , ????????? ???????? ? ????????? ???? ?????? ???????? ?????? ???????????? T-??????? , ?? ?? ?????? ?? ???????????? ?-?????? , ? ?? ????? ??? ????-LAG-3 ????????-??????????? ????? ??? ???????????? T-??????? (?? ???? ???????????? ????????????? ??????? ?? ?????????????? LAG-3 ⁺ ???????), ??? ? ???????????? ?????????????? ???????-??????????? ???????????? ?????????? ???????????? ?-?????? . ????? ?????, ????????????? ??????? ????? ???????? ???????? ? LAG3 ? ?????????? ? CTLA-4 ??? PD-1 .

????????-???????? ? LAG3 ????? ??????????? ??? ?????????? ????????? ??????. ? ???????, ???????????? ???? ??????, ????????? GSK2831781, ?????????? ??????????? ????????? ??? ??????? ????????????? ??????????? ???????? .

??????????

? - Ensembl , May 2017
? - Ensembl , May 2017
???????????? ????? ?????????????????? ??????????, ???????????? ??????????? ?????????? ??? .
???????????? ????? ?????????????????? ??????????, ???????????? ??????????? ?????????? ??? .
? .
? Triebel F, Jitsukawa S, Baixeras E, Roman-Roman S, Genevee C, Viegas-Pequignot E, Hercend T (May 1990). . The Journal of Experimental Medicine . 171 (5): 1393—405. doi : . PMC . PMID .
Mason D, André P, Bensussan A, Buckley C, Civin C, Clark E, de Haas M, Goyert S, Hadam M, Hart D, Horejsí V, Meuer S, Morrissey J, Schwartz-Albiez R, Shaw S, Simmons D, Uguccioni M, van der Schoot E, Vivier E, Zola H (Nov 2001). "CD antigens 2001". Journal of Leukocyte Biology . 70 (5): 685—90. PMID .
? Syn, Nicholas L; Teng, Michele W L; Mok, Tony S K; Soo, Ross A (December 2017). "De-novo and acquired resistance to immune checkpoint targeting". The Lancet Oncology (????.) . 18 (12): e731—e741. doi : . PMID .
? Grosso JF, Kelleher CC, Harris TJ, Maris CH, Hipkiss EL, De Marzo A, Anders R, Netto G, Getnet D, Bruno TC, Goldberg MV, Pardoll DM, Drake CG (Nov 2007). . The Journal of Clinical Investigation . 117 (11): 3383—92. doi : . PMC . PMID .
Kim SS, Kim SH, Kang HS, Chung HY, Choi I, Cheon YP, Lee KH, Lee DM, Park J, Lee SY, Chun T (Jan 2010). "Molecular cloning and expression analysis of pig lymphocyte activation gene-3 (LAG-3; CD223)". Veterinary Immunology and Immunopathology . 133 (1): 72—9. doi : . PMID .
Huard B, Gaulard P, Faure F, Hercend T, Triebel F (January 1, 1994). . Immunogenetics . 39 (3): 213—7. doi : . PMID . S2CID .
Kisielow M, Kisielow J, Capoferri-Sollami G, Karjalainen K (Jul 2005). . European Journal of Immunology . 35 (7): 2081—8. doi : . PMID . S2CID .
Workman CJ, Wang Y, El Kasmi KC, Pardoll DM, Murray PJ, Drake CG, Vignali DA (Feb 2009). . Journal of Immunology . 182 (4): 1885—91. doi : . PMC . PMID .
Huard B, Prigent P, Tournier M, Bruniquel D, Triebel F (Sep 1995). "CD4/major histocompatibility complex class II interaction analyzed with CD4- and lymphocyte activation gene-3 (LAG-3)-Ig fusion proteins". European Journal of Immunology . 25 (9): 2718—21. doi : . PMID . S2CID .
Workman CJ, Vignali DA (Apr 2003). . European Journal of Immunology . 33 (4): 970—9. doi : . PMID . S2CID .
Workman CJ, Cauley LS, Kim IJ, Blackman MA, Woodland DL, Vignali DA (May 2004). . Journal of Immunology . 172 (9): 5450—5. doi : . PMID .
Huang CT, Workman CJ, Flies D, Pan X, Marson AL, Zhou G, Hipkiss EL, Ravi S, Kowalski J, Levitsky HI, Powell JD, Pardoll DM, Drake CG, Vignali DA (Oct 2004). . Immunity . 21 (4): 503—13. doi : . PMID .
Wang J, Sanmamed MF, Datar I, Su TT, Ji L, Sun J, Chen L, Chen Y, Zhu G, Yin W, Zheng L, Zhou T, Badri T, Yao S, Zhu S, Boto A, Sznol M, Melero I, Vignali DA, Schalper K, Chen L (Jan 2019). . Cell . 176 (1—2): 334—47. doi : . PMC . PMID .
Blackburn SD, Shin H, Haining WN, Zou T, Workman CJ, Polley A, Betts MR, Freeman GJ, Vignali DA, Wherry EJ (Jan 2009). . Nature Immunology . 10 (1): 29—37. doi : . PMC . PMID .
Andreae S, Piras F, Burdin N, Triebel F (Apr 2002). . Journal of Immunology . 168 (8): 3874—80. doi : . PMID .
. www.immutep.com . ???? ?????????: 9 ??????? 2019. 9 ??????? 2019 ????.
Avice M; Sarfati M; Triebel F; Delespesse G; Demeure CE. (March 1, 1999). . J. Immunol . 162 (5): 2748—53. PMID .
? Clinical trial number for "An Investigational Immuno-therapy Study of Relatlimab Plus Nivolumab Compared to Various Standard-of-Care Therapies in Previously Treated Participants With Recurrent, Advanced or Metastatic Gastric Cancer or Gastroesophageal Junction Adenocarcinoma" at
. Tesaro web site . ???? ?????????: 4 ????? 2021. 7 ?????? 2016 ????.
. Immutep LAG-3. ???? ?????????: 1 ???? 2015. ???????????? ?? 1 ???? 2015 ????.
. ???? ?????????: 4 ????? 2021. 10 ?????? 2021 ????.

??????????

Triebel F (Dec 2003). "LAG-3: a regulator of T-cell and DC responses and its use in therapeutic vaccination". Trends in Immunology . 24 (12): 619—22. doi : . PMID .
Baixeras E, Huard B, Miossec C, Jitsukawa S, Martin M, Hercend T, Auffray C, Triebel F, Piatier-Tonneau D (Aug 1992). . The Journal of Experimental Medicine . 176 (2): 327—37. doi : . PMC . PMID .
Triebel F, Jitsukawa S, Baixeras E, Roman-Roman S, Genevee C, Viegas-Pequignot E, Hercend T (May 1990). . The Journal of Experimental Medicine . 171 (5): 1393—405. doi : . PMC . PMID .
Blum MD, Wong GT, Higgins KM, Sunshine MJ, Lacy E (May 1993). . The Journal of Experimental Medicine . 177 (5): 1343—58. doi : . PMC . PMID .
Huard B, Mastrangeli R, Prigent P, Bruniquel D, Donini S, El-Tayar N, Maigret B, Dréano M, Triebel F (May 1997). . Proceedings of the National Academy of Sciences of the United States of America . 94 (11): 5744—9. Bibcode : . doi : . PMC . PMID .
Bruniquel D, Borie N, Triebel F (1998). "Genomic organization of the human LAG-3/CD4 locus". Immunogenetics . 47 (1): 96—8. doi : . PMID . S2CID .
Bruniquel D, Borie N, Hannier S, Triebel F (Jul 1998). "Regulation of expression of the human lymphocyte activation gene-3 (LAG-3) molecule, a ligand for MHC class II". Immunogenetics . 48 (2): 116—24. doi : . PMID . S2CID .
Hannier S, Tournier M, Bismuth G, Triebel F (Oct 1998). "CD3/TCR complex-associated lymphocyte activation gene-3 molecules inhibit CD3/TCR signaling". Journal of Immunology . 161 (8): 4058—65. PMID .
Hannier S, Triebel F (Nov 1999). . International Immunology . 11 (11): 1745—52. doi : . PMID .
Iouzalen N, Andreae S, Hannier S, Triebel F (Oct 2001). "LAP, a lymphocyte activation gene-3 (LAG-3)-associated protein that binds to a repeated EP motif in the intracellular region of LAG-3, may participate in the down-regulation of the CD3/TCR activation pathway". European Journal of Immunology . 31 (10): 2885—91. doi : . PMID .
Andreae S, Piras F, Burdin N, Triebel F (Apr 2002). . Journal of Immunology . 168 (8): 3874—80. doi : . PMID .
Andreae S, Buisson S, Triebel F (Sep 2003). . Blood . 102 (6): 2130—7. doi : . PMID .
Cai XF, Tao Z, Yan ZQ, Yang SL, Gong Y (Apr 2003). "Molecular cloning, characterisation and tissue-specific expression of human LAG3, a member of the novel Lag1 protein family". DNA Sequence . 14 (2): 79—86. doi : . PMID . S2CID .
Gandhi MK, Lambley E, Duraiswamy J, Dua U, Smith C, Elliott S, Gill D, Marlton P, Seymour J, Khanna R (Oct 2006). . Blood . 108 (7): 2280—9. doi : . PMID .
Lundmark F, Harbo HF, Celius EG, Saarela J, Datta P, Oturai A, Lindgren CM, Masterman T, Salter H, Hillert J (Nov 2006). "Association analysis of the LAG3 and CD4 genes in multiple sclerosis in two independent populations". Journal of Neuroimmunology . 180 (1—2): 193—8. doi : . PMID . S2CID .

[refGRCh38EnsemblENSG00000089692-1] ? - Ensembl , May 2017

[refGRCm38EnsemblENSMUSG00000030124-2] ? - Ensembl , May 2017

[3] ???????????? ????? ?????????????????? ??????????, ???????????? ??????????? ?????????? ??? .

[4] ???????????? ????? ?????????????????? ??????????, ???????????? ??????????? ?????????? ??? .

[entrez-5] ? .

[Triebel_F,_Jitsukawa_S,_Baixeras_E,_Roman-Roman_S,_Genevee_C,_Viegas-Pequignot_E,_Hercend_T_1393–405-6] ? Triebel F, Jitsukawa S, Baixeras E, Roman-Roman S, Genevee C, Viegas-Pequignot E, Hercend T (May 1990). . The Journal of Experimental Medicine . 171 (5): 1393—405. doi : . PMC . PMID .

[7] Mason D, André P, Bensussan A, Buckley C, Civin C, Clark E, de Haas M, Goyert S, Hadam M, Hart D, Horejsí V, Meuer S, Morrissey J, Schwartz-Albiez R, Shaw S, Simmons D, Uguccioni M, van der Schoot E, Vivier E, Zola H (Nov 2001). "CD antigens 2001". Journal of Leukocyte Biology . 70 (5): 685—90. PMID .

[:0-8] ? Syn, Nicholas L; Teng, Michele W L; Mok, Tony S K; Soo, Ross A (December 2017). "De-novo and acquired resistance to immune checkpoint targeting". The Lancet Oncology (????.) . 18 (12): e731—e741. doi : . PMID .

[Grosso_JF,_Kelleher_CC,_Harris_TJ,_Maris_CH,_Hipkiss_EL,_De_Marzo_A,_Anders_R,_Netto_G,_Getnet_D,_Bruno_TC,_Goldberg_MV,_Pardoll_DM,_Drake_CG._3383–92-9] ? Grosso JF, Kelleher CC, Harris TJ, Maris CH, Hipkiss EL, De Marzo A, Anders R, Netto G, Getnet D, Bruno TC, Goldberg MV, Pardoll DM, Drake CG (Nov 2007). . The Journal of Clinical Investigation . 117 (11): 3383—92. doi : . PMC . PMID .

[10] Kim SS, Kim SH, Kang HS, Chung HY, Choi I, Cheon YP, Lee KH, Lee DM, Park J, Lee SY, Chun T (Jan 2010). "Molecular cloning and expression analysis of pig lymphocyte activation gene-3 (LAG-3; CD223)". Veterinary Immunology and Immunopathology . 133 (1): 72—9. doi : . PMID .

[11] Huard B, Gaulard P, Faure F, Hercend T, Triebel F (January 1, 1994). . Immunogenetics . 39 (3): 213—7. doi : . PMID . S2CID .

[ReferenceA-12] Kisielow M, Kisielow J, Capoferri-Sollami G, Karjalainen K (Jul 2005). . European Journal of Immunology . 35 (7): 2081—8. doi : . PMID . S2CID .

[ReferenceB-13] Workman CJ, Wang Y, El Kasmi KC, Pardoll DM, Murray PJ, Drake CG, Vignali DA (Feb 2009). . Journal of Immunology . 182 (4): 1885—91. doi : . PMC . PMID .

[Huard_B,_Prigent_P,_Tournier_M,_Bruniquel_D,_Triebel_F._2718–21-14] Huard B, Prigent P, Tournier M, Bruniquel D, Triebel F (Sep 1995). "CD4/major histocompatibility complex class II interaction analyzed with CD4- and lymphocyte activation gene-3 (LAG-3)-Ig fusion proteins". European Journal of Immunology . 25 (9): 2718—21. doi : . PMID . S2CID .

[Workman_CJ,_Vignali_DA._:970–9-15] Workman CJ, Vignali DA (Apr 2003). . European Journal of Immunology . 33 (4): 970—9. doi : . PMID . S2CID .

[Workman_CJ,_Cauley_LS,_Kim_IJ,_Blackman_MA,_Woodland_DL,_Vignali_DA_5450–5-16] Workman CJ, Cauley LS, Kim IJ, Blackman MA, Woodland DL, Vignali DA (May 2004). . Journal of Immunology . 172 (9): 5450—5. doi : . PMID .

[Huang_CT,_Workman_CJ,_Flies_D,_Pan_X,_Marson_AL,_Zhou_G,_Hipkiss_EL,_Ravi_S,_Kowalski_J,_Levitsky_HI,_Powell_JD,_Pardoll_DM,_Drake_CG,_Vignali_DA_503–13-17] Huang CT, Workman CJ, Flies D, Pan X, Marson AL, Zhou G, Hipkiss EL, Ravi S, Kowalski J, Levitsky HI, Powell JD, Pardoll DM, Drake CG, Vignali DA (Oct 2004). . Immunity . 21 (4): 503—13. doi : . PMID .

[Wang_J,_Sanmamed_MF,_Datar_I,_Su_TT,_Ji_L,_Sun_J,_Chen_L,_Chen_Y,_Zhu_G,_Yin_W,_Zheng_L,_Zhou_T,_Badri_T,_Yao_S,_Zhu_S,_Boto_A,_Sznol_M,_Melero_I,_Vignali_DA,_Schalper_K,_Chen_L._334-347-18] Wang J, Sanmamed MF, Datar I, Su TT, Ji L, Sun J, Chen L, Chen Y, Zhu G, Yin W, Zheng L, Zhou T, Badri T, Yao S, Zhu S, Boto A, Sznol M, Melero I, Vignali DA, Schalper K, Chen L (Jan 2019). . Cell . 176 (1—2): 334—47. doi : . PMC . PMID .

[19] Blackburn SD, Shin H, Haining WN, Zou T, Workman CJ, Polley A, Betts MR, Freeman GJ, Vignali DA, Wherry EJ (Jan 2009). . Nature Immunology . 10 (1): 29—37. doi : . PMC . PMID .

[20] Andreae S, Piras F, Burdin N, Triebel F (Apr 2002). . Journal of Immunology . 168 (8): 3874—80. doi : . PMID .

[21] . www.immutep.com . ???? ?????????: 9 ??????? 2019. 9 ??????? 2019 ????.

[Avice1999-22] Avice M; Sarfati M; Triebel F; Delespesse G; Demeure CE. (March 1, 1999). . J. Immunol . 162 (5): 2748—53. PMID .

[GI_study-23] ? Clinical trial number for "An Investigational Immuno-therapy Study of Relatlimab Plus Nivolumab Compared to Various Standard-of-Care Therapies in Previously Treated Participants With Recurrent, Advanced or Metastatic Gastric Cancer or Gastroesophageal Junction Adenocarcinoma" at

[24] . Tesaro web site . ???? ?????????: 4 ????? 2021. 7 ?????? 2016 ????.

[25] . Immutep LAG-3. ???? ?????????: 1 ???? 2015. ???????????? ?? 1 ???? 2015 ????.

[26] . ???? ?????????: 4 ????? 2021. 10 ?????? 2021 ????.

????? : ???????? ???????????????
1-50	CD1 ( , 1A , 1D , 1E ) CD2 CD3 ( ? , ? , ? ) CD4 CD5 CD6 CD7 CD8 ( ) CD9 CD10 CD11 ( a , b , c , d ) CD13 CD14 CD15 CD16 ( A , B ) CD18 CD19 CD20 CD21 CD22 CD23 CD24 CD25 CD26 CD27 CD28 CD29 CD30 CD31 CD32 ( , ) CD33 CD34 CD36 CD37 CD38 CD39 CD40 CD41 CD42 ( a , b , c , d ) CD43 CD44 CD45 CD46 CD47 CD48 CD49 ( a , b , c , d , e , f ) CD50
51-100	CD51 CD52 CD53 CD54 CD55 CD56 CD57 CD58 CD59 CD61 CD62 ( E , L , P ) CD63 CD64 ( A , , ) CD66 ( a , b , c , d , e , f ) CD68 CD69 CD70 CD71 CD72 CD73 CD74 CD79 ( a , b ) CD80 CD81 CD82 CD83 CD84 CD85 ( a , d , e , h , j , k ) CD86 CD87 CD88 CD89 CD90 CD91 CD92 CD93 CD94 CD95 CD96 CD97 CD98 CD99 CD100
101-150	CD101 CD102 CD103 CD104 CD105 CD106 CD107 ( a , b ) CD108 CD109 CD111 CD112 CD113 CD116 CD117 CD120 ( a , b ) CD121 ( , ) CD123 CD125 CD131 CD132 CD133 CD134 CD135 CD136 CD137 CD138 CD140b CD141 CD142 CD143 CD144 CD146 CD147 CD148 CD150
151-200	CD151 CD152 CD153 CD154 CD155 CD156 ( a , b , c ) CD157 CD158 ( a , d , e , i , k ) CD159 ( , ) CD160 CD161 CD162 CD163 CD164 CD166 CD167 ( a , b ) CD169 CD170 CD172 ( , , ) CD174 CD177 CD179 ( a , b ) CD181 CD182 CD183 CD184 CD185 CD186 CD191 CD192 CD193 CD194 CD195 CD196 CD197 CDw198 CDw199 CD200
201-250	CD201 CD202b CD204 CD205 CD206 CD207 CD208 CD209 CDw210 ( a , b ) CD212 CD213a ( , ) CD217 CD218 ( a , b ) CD220 CD224 CD225 CD226 CD227 CD228 CD229 CD230 CD235 ( , ) CD238 CD239 CD240CE CD240D CD241 CD243 CD244 CD246 CD247 CD248 CD249
251-300	CD252 CD253 CD254 CD256 CD257 CD258 CD261 CD262 CD263 CD264 CD265 CD266 CD267 CD268 CD269 CD270 CD271 CD272 CD273 CD274 CD275 CD276 CD278 CD279 CD280 CD281 CD282 CD283 CD284 CD286 CD288 CD289 CD290 CD292 CDw293 CD294 CD295 CD297 CD298 CD299
301-350	CD300A CD301 CD302 CD303 CD304 CD305 CD306 CD307 CD309 CD312 CD314 CD315 CD316 CD317 CD318 CD319 CD320 CD321 CD322 CD324 CD325 CD326 CD328 CD329 CD331 CD332 CD333 CD334 CD335 CD336 CD337 CD338 CD339 CD340 CD344 CD349 CD350
351-400	CD351 CD352 CD353 CD354 CD357 CD358 CD360 CD361 CD362 CD363 CD364 CD365 CD366 CD367 CD369 CD370 CD371

Interested Article - LAG3

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Same as LAG3

VPREB1

LAMP1

Ангиотензинпревращающий фермент

Инсулиновый рецептор

CCR5

Тетерин (белок)

CXCR4

CCR2

ICAM-1

LAMP2

PRNP

CD16

Интегрин бета-2

Интегрин бета-1

CCR1

CCR3

CD5 (белок)

CD19

CD20

CD22

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